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Cell Biology:

Cell Biology Semester II

Living cells probably arose on earth about 3.5 billion years ago by spontaneous reactions between molecules in an environment that was far from chemical equilibrium. Cells Vary Enormously in Appearance and Function:

Living cells probably arose on earth about 3.5 billion years ago by spontaneous reactions between molecules in an environment that was far from chemical equilibrium. Cells Vary Enormously in Appearance and Function Lactobacillus in a piece of cheese—is a few micrometers, or mm, in length A frog’s egg—which is also a single cell—has a diameter of about 1 millimeter.

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A human white blood cell (a neutrophil) approaching and engulfing a red blood cell. 10 μ m A tiny bacterium, Bdellovibrio bacteriovorus, that uses a single terminal flagellum to propel itself. It attacks, kills, and feeds on larger bacteria. 0.5 μ m A nerve cell from the cerebellum (a part of the brain that controls movement). This cell has a huge branching tree of processes, through which it receives signals from as many as 100,000 other nerve cells. 100 μ m

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Procaryotes Eucaryotes bacteria and cyanobacteria protists, fungi, plants, and animals Cell size generally 1 to 10 •m in linear generally 5 to 100 •m in linear Metabolism anaerobic or aerobic aerobic Organelles few or none nucleus, mitochondria , chloroplasts,endoplasmic reticulum , DNA circular DNA in cytoplasm very long linear DNA molecules containing many noncoding regions; bounded by nuclear envelope RNA and protein synthesized in same RNA synthesized and Compartment processed in nucleus; proteins synthesized in cytoplasm

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Cytoplasm no cytoskeleton: cytoplasmic streaming,endocytosis, and cytoskeleton composed of exocytosis all absent protein filaments; cytoplasmic streaming; endocytosis and exocytosis Cell division: chromosomes chromosomes pulled apart by pulled apart by attachments to cytoskeletal spindle apparatus plasma membrane Cellular organization mainly unicellular mainly multicellular, with differentiation of many types

Plasma membrane:

Plasma membrane

Cytoskeleton:

Cytoskeleton Although cells sometimes are spherical, they more commonly have more elaborate shapes due to their internal skeletons and external attachments. Three types of protein filaments, organized into networks and bundles, form the cytoskeleton within animal cells (Figure 1-15). The cytoskeleton prevents the plasma membrane of animal cells from relaxing into a sphere; it also functions in cell locomotion and the intracellular transport of vesicles, chromosomes, and macromolecules. The cytoskeleton can be linked through the cell surface to the extracellular matrix or to the cytoskeleton of other cells, thus helping to form tissues. Intermediate filaments Microtubules Microfilaments

Mitochondria:

Mitochondria

Ribosome:

Ribosome Fig: Ribosome docking onto rough ER

Centriole:

Centriole

Golgi apparatus:

Golgi apparatus

Lysosome:

Lysosome

Slide 15:

The nucleus is the most prominent organelle in this thin section of a mammalian cell examined in the electron microscope. Individual chromosomes are not visible because the DNA is dispersed as fine threads throughout the nucleus at this stage of the cell’s growth.

Nuclear membrane:

Nuclear membrane

Inside Nuclelus:

Inside Nuclelus

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condensed chromosomes nuclear envelope Chromosomes become visible when a cell is about to divide. As a cell prepares to divide, its DNA condenses into threadlike chromosomes that can be distinguished in the light microscope.

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The electron microscope reveals the folds in the mitochondrial membrane. (A) A cross section of a mitochondrion. (B) This threedimensional representation of the arrangement of the mitochondrial membranes shows the smooth outer membrane and the highly convoluted inner membrane. The inner membrane contains most of the proteins responsible for cellular respiration, and it is highly folded to provide a large surface area for this activity .

Cell cycle :

Cell cycle The eukaryotic cell cycle contains four major phases (see Figure 1-4). The S phase is when DNA synthesis occurs to replicate the chromosomes by creating identical sister chromatids . The period between S phase and the beginning of mitosis ( M phase ) is a gap, or growth period, designated G2 phase . Another gap or growth period called the G1 phase , occurs between the M and S phases to complete the cycle. Mitosis consists of four consecutive phases: prophase , metaphase , anaphase , and telophase (see Figure 1-5). During prophase, each chromosome shortens and thickens by supercoiling on itself again and again.

CELL JUNCTIONS:

CELL JUNCTIONS

A Functional Classification of Cell Junctions:

A Functional Classification of Cell Junctions 1. Occluding junctions (tight junctions) which can seal cells together in an epithelial cell sheet in a way that prevents even small molecules from leaking from one side of the sheet to the other 2. Anchoring junctions, which mechanically attach cells (and their cytoskeletons) to their neighbors or to the extracellular matrix; a. actin filament attachment sites i. cell-cell adherens junctions (e.g., adhesion belts) ii. cell-matrix adherens junctions (e.g., focal contacts) iii. septate junctions (invertebrates only) b. intermediate filament attachment sites i. cell-cell (desmosomes) ;ii. cell-matrix (hemidesmosomes) 3. Communicating junctions, which mediate the passage of chemical or electrical signals from one interacting cell to its partner. a. gap junctions b. chemical synapses c. plasmodesmata (plants only)

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The role of tight junctions in transcellular transport.

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Transport proteins are confined to different regions of the plasma membrane in epithelial cells of the small intestine. This segregation permits a vectorial transfer of nutrients across the epithelial sheet from the gut lumen to the blood. In the example shown, glucose is actively transported into the cell by Na+-driven glucose symports at the apical surface, and it diffuses out of the cell by facilitated diffusion mediated by glucose carriers in the basolateral membrane. Tight junctions are thought to confine the transport proteins to their appropriate membrane domains by acting as diffusion barriers within the lipid bilayer of the plasma membrane; these junctions also block the backflow of glucose from the basal side of the epithelium into the gut lumen.

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It is postulated that the sealing strands that hold adjacent plasma membranes together are formed by continuous strands of transmembrane junctional proteins, which make contact across the intercellular space and create a seal. In this schematic the cytoplasmic half of one membrane has been peeled back by the artist to expose the protein strands. Two peripheral proteins associated with the cytoplasmic side of tight junctions have been characterized, but the putative transmembrane protein has not yet been identified. In freeze-fracture electron microscopy the tight-junction proteins would remain with the cytoplasmic (P face) half of the lipid bilayer to give the pattern of intramembrane particles, instead of staying in the other half as shown here

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Construction of an anchoring junction. Highly schematized drawing showing the two classes of proteins that constitute such a junction: intracellular attachment proteins and transmembrane linker proteins.

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Anchoring junctions in an epithelial tissue. Highly schematized drawing of how such junctions join cytoskeletal filaments from cell to cell and from cell to extracellular matrix.

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The actin filaments are joined from cell to cell by transmembrane linker proteins (cadherins), whose extracellular domain binds to the extracellular domain of an identical cadherin molecule on the adjacent cell Adhesion belts between epithelial cells in the small intestine. This beltlike anchoring junction encircles each of the interacting cells. Its most obvious feature is a contractile bundle of actin filaments running along the cytoplasmic surface of the junctional plasma membrane.

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Desmosomes. (A) An electron micrograph of three desmosomes between two epithelial cells in theintestine of a rat. (B) An electron micrograph of a single desmosome between two epidermal cells in a developing newt, showing clearly the attachment of intermediate filaments. (C) A schematic drawing of a desmosome. On the cytoplasmic surface of each interacting plasma membrane is a dense plaque composed of a mixture of intracellular attachment proteins (including plakoglobin and desmoplakins ). Each plaque is associated with a thick network of keratin filaments, which are attached to the surface of the plaque. Transmembrane linker proteins, which belong to the cadherin family of cell-cell adhesion molecules, bind to the plaques and interact through their extracellular domains to hold the adjacent membranes together by a Ca2+-dependent mechanism

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The distribution of desmosomes and hemidesmosomes in epithelial cells of the small intestine. The keratin filament networks of adjacent cells are indirectly connected to one another through desmosomes and to the basal lamina through hemidesmosomes.

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A model of a gap junction. The drawing shows the interacting plasma membranes of two adjacent cells. The apposed lipid bilayers ( red ) are penetrated by protein assemblies called connexons ( green ), each of which is thought to be formed by six identical protein subunits (called connexins ). Two connexons join across the intercellular gap to form a continuous aqueous channel connecting the two cells.

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A proposed model for how gap-junction channels may close in response to a rise in Ca2+ or a fall in pH in the cytosol. A small rotation of each subunit closes the channel. The model is based on an image analysis of electron micrographs of rapidly frozen tissue in which the structure of gap junction channels in their presumed open state was compared with their structure in a Ca2+-induced closed state.

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Summary of the various cell junctions found in animal cell epithelia. This drawing is based on epithelial cells of the small intestine.

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The absorption of nutrients through the small intestine occurs through two main mechanisms, active and passive transport.

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Active transport: Active transport involves the uptake of the active ingredient through specific channels on the surface of the epithelial cells. Active transport is the main mechanism by which cell captures and absorb highly soluble minerals like calcium and iron. This active uptake is controlled by hormones that regulate the concentration of minerals and other nutrients in the body.

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Passive transport: Passive transport occurs by a simple diffusion across the epithelial tissue. Most hydrophobic compounds are highly permeable through the intestines and transport using passive and active diffusion. However highly hydrophilic substances tend to have low permeability and absorb via active transport.

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M cells: Lymphoepithelial cells having unique characteristics. The term M-cells to reflect their ‘membranous’ appearance under scanning electron microscopy with irregular shaped ‘microfolds’ compared to classical villi on adjacent enterocytes. The most noticeable feature is their active transport (by a phagocytic mode of transport) of a wide variety of inert material from the gut lumen towards the follicles, from where particles can migrate to the blood via the mesentery nodes and the thoracic lymph duct.

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Chemiosmotic coupling. Energy from sunlight or the oxidation of foodstuffs is first used to create an electrochemical proton gradient across a membrane. This gradient serves as a versatile energy store and is used to drive a variety of reactions in mitochondria, chloroplasts, and bacteria.

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Chemiosmosis is the movement of ions across a selectively-permeable membrane, down their electrochemical gradient. More specifically, it relates to the generation of ATP by the movement of hydrogen ions across a membrane during cellular respiration. Proton gradient has two components : the chemical components the proton concentration or pH gradient; an electric potential positive charge on the cytosolic side An Ion gradient has potential energy and can be used to power chemical reactions when the ions pass through a channel (red). Hydrogen ions (protons) will diffuse from an area of high proton concentration to an area of lower proton concentration. Peter Mitchell proposed that an electrochemical concentration gradient of protons across a membrane could be harnessed to make ATP. He linked this process to osmosis, the diffusion of water across a membrane, which is why it is called chemiosmosis. A total of 10 protons are ejected from the mitochondrial matrix per 2 electrons transferred from NADH to oxygen via the respiratory chain. pH 7 pH 8 Matrix Intermembrane space H+ H+ H+ H+ H+ H+ H+ +++++++++++++ Concentration gradient Electric gradient - - - - - - - H+ H+ H+ cytosol

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e- pairs enter The ETC from NADPH in complex I The e- are then Transferred to co-Q Which carries e- Through the membrane To complex III e- are trnsferred to Cyt c, which carries e- to complexIV Complex IV Transfers e- to Molecular O

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Complex I (NADH Dehydrogenase) transports 4H+ out of the mitochondrial matrix per 2e- transferred from NADH to coenzyme Q. Direct coupling of transmembrane proton flux and electron transfer is unlikely, because the electron-transferring prosthetic groups, FMN and iron-sulfur centers, are all located in the peripheral domain of complex I (see notes on electron transfer chain). Thus it is assumed that protein conformational changes are involved in H+ transport, as with an ion pump. The e- transfer in I, III and IVare associated with decrease in free energy which is used to pump protons From the matrix to the intermediate space. This establishes a proton gradient acress the inner membrane The energy stored in the proton gradientis then used drive ATP synthesis as the proton flow back to the matrix Through complex V

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The Chemiosmotic Theory states that coupling of electron transfer to ATP synthesis is indirect, via a H+ electrochemical gradient: Respiration: Spontaneous electron transfer through complexes I, III, and IV is coupled to non-spontaneous H+ ejection from the mitochondrial matrix. H+ ejection creates a membrane potential (DY, negative in the matrix) and a pH gradient (DpH, alkaline in the matrix). F1Fo ATP Synthase: Non-spontaneous ATP synthesis is coupled to spontaneous H+ transport into the matrix compartment. The pH and electrical gradients created by respiration are together the driving force for H+ uptake. Return of protons to the matrix via Fo "uses up" the pH and electrical gradients.

Electrons from succinate enter the chain via FADH2 into Co-Q. The transfer of e- from FADH2 to CoQ is not associated with significant decrease in free energy so protons are pumped across the membrane at II:

Electrons from succinate enter the chain via FADH2 into Co-Q. The transfer of e- from FADH2 to CoQ is not associated with significant decrease in free energy so protons are pumped across the membrane at II Succinate FADH2 II III Q 2e- Cyt C

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ATP synthase. As indicated, the F1ATPase portion is formed from multiple subunits The mitochondrial ATP synthase 9complex V) Consist of two multisubunit components F0 and F1. F0 spans the lipid bilayer forming a channel through which protons can cross the membrane. F1 harvests the free energy derived from proton movement down the electrochemical gradient by catalyzing the synthesis of ATP

Endoplasmic Reticulum:

Endoplasmic Reticulum All eucaryotic cells have an endoplasmic reticulum (ER). Its membrane typically constitutes more than half of the total membrane of an average animal cell (see Table 12-2). It is organized into a netlike labyrinth of branching tubules and flattened sacs extending throughout the cytosol. The tubules and sacs are all thought to interconnect, so that the ER membrane forms a continuous sheet enclosing a single internal space. This highly convoluted space is called the ER lumen or the ER cisternal space, and it often occupies more than 10% of the total cell volume. The ER membrane separates the ER lumen from the cytosol, and it mediates the selective transfer of molecules between these two compartments. The ER captures selected proteins from the cytosol as they are being synthesized. These proteins are of two types: (1) transmembrane proteins, which are only partly translocated across the ER membrane and become embedded in it, and (2) water-soluble proteins, which are fully translocated across the ER membrane and are released into the ER lumen. Some of the transmembrane proteins will remain in the ER, but many are destined to reside in the plasma membrane or the membrane of another organelle; the water-soluble proteins are destined either for the lumen of an organelle or for secretion. All of these proteins, regardless of their subsequent fate, are directed to the ER membrane by the same kind of signal peptide and are translocated across it by the same mechanism. In mammalian cells the import of proteins into the ER begins before the polypeptide chain is completely synthesized - that is, it occurs co-translationally.

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This distinguishes the process from the import of proteins into mitochondria, chloroplasts, nuclei, and peroxisomes, which is posttranslational and requires different signal peptides. Since one end of the protein is usually translocated into the ER as the rest of the polypeptide chain is being made, the protein is never released into the cytosol and therefore is never in danger of folding up before reaching the translocator in the membrane. In contrast to the posttranslational import of proteins into the mitochondria and chloroplasts, cytosolic chaperonins are therefore not required to keep the protein unfolded. The ribosome that is synthesizing the protein is directly attached to the ER membrane. These membrane-bound ribosomes coat the surface of the ER, creating regions termed rough endoplasmic reticulum. There are, therefore, two spatially separate populations of ribosomes in the cytosol. Membrane bound ribosomes, attached to the cytosolic side of the ER membrane, are engaged in the synthesis of proteins that are being concurrently translocated into the ER. Free ribosomes, unattached to any membrane, make all other proteins encoded by the nuclear genome. Membrane-bound and free ribosomes are structurally and functionally identical. They differ only in the proteins they are making at any given time. When a ribosome happens to be making a protein with an ER signal peptide, the signal directs the ribosome to the ER membrane. Since many ribosomes can bind to a single mRNA molecule, a polyribosome is usually formed, which becomes attached to the ER membrane via the signal peptides on multiple growing polypeptide chains The individual ribosomes associated with such an mRNA molecule can return to the cytosol when they finish translation near the 3' end of the mRNA molecule.

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The mRNA itself, however, tends to remain attached to the ER membrane by a changing population of ribosomes that are also held at the membrane by a ribosome receptor that helps to bind it there. In contrast, if an mRNA molecule encodes a protein that lacks an ER signal peptide, the polyribosome that forms remains free in the cytosol and its protein product is discharged there. Therefore, only those mRNA molecules that encode proteins with an ER signal peptide bind to rough ER membranes; those mRNA molecules that encode all other proteins remain free in the cytosol. The individual ribosomal subunits are thought to move randomly between these two segregated populations of mRNA molecules ( Figure 12-33).

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FUNCTIONS 1.The ER plays a central part in lipid and protein biosynthesis. Its membrane is the site of production of all the transmembrane roteins and lipids for most of the cell's organelles, including the ER itself, the Golgi apparatus, lysosomes, endosomes, secretory vesicles, and the plasma membrane. The ER membrane also makes a major contribution to mitochondrial and peroxisomal membranes by producing most of their lipids. In addition, almost all of the proteins that will be secreted to the cell exterior - as well as those destined for the lumen of the ER, Golgi apparatus, or lysosomes - are initially delivered to the ER lumen.

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The original signal hypothesis. A simplified view of protein translocation across the n ER membrane, as originally proposed. When the signal peptide emerges from the ribosome, it directs the ribosome to a receptor protein on the ER membrane. As it is synthesized, the polypeptide is postulated to be translocated across the ER membrane through a protein pore associated with the receptor. The signal peptide is clipped off during translation by a signal peptidase, and the mature protein is released into the lumen of the ER immediately after being synthesized.

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the biosynthetic-secretory pathway leads outward from the ER toward the Golgi apparatus and cell surface, with a side route leading to lysosomes, while the endocytic pathway leads inward toward endosomes and lysosomes from the plasma membrane To perform its function, each transport vesicle that buds from a compartment must take up only the appropriate proteins and must fuse only with the appropriate target membrane. A vesicle carrying cargo from the Golgi apparatus to the plasma membrane, for example, must exclude proteins that are to stay in the Golgi apparatus, and it must fuse only with the plasma membrane and not with any other organelle. While participating in this constant flow of membrane components, each organelle must maintain its own distinct identity. In this chapter we consider the function of the Golgi apparatus, lysosomes, secretory vesicles, and endosomes, and we trace the pathways by which these organelles are interconnected. FIG: The secretory and endocytic pathways. In this "road map" of biosynthetic protein traffic, both the secretory and endocytic pathways are colored.

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Vesicular transport. Transport vesicles bud off from one compartment and fuse with another.

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The intracellular compartments of the eucaryotic cell involved in the biosynthetic secretory and endocytic pathways. Each compartment encloses a space that is topologically equivalent to the outside of the cell, and they all communicate with one another by means of transport vesicles. In the biosynthetic-secretory pathway ( red arrows ) protein molecules are transported from the ER to the plasma membrane or (via late endosomes) to lysosomes. In the endocytic pathway ( green arrows ) molecules are ingested in vesicles derived from the plasma membrane and delivered to early endosomes and then (via late endosomes) to lysosomes . Many endocytosed molecules are retrieved from early endosomes and returned to the cell surface for reuse; similarly, some molecules are retrieved from the late endosome and returned to the Golgi apparatus, and some are retrieved from the Golgi apparatus and returned to the ER. All of these retrieval pathways are shown with blue arrows.

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Golgi which is a major site of carbohydrate synthesis as well as a sorting and dispatching station for the products of the ER. Many of the cell's polysaccharides are made in the Golgi apparatus, including the pectin and hemicellulose of the plant cell wall and most of the glycosaminoglycans of the extracellular matrix in animals. But the Golgi apparatus also lies on the exit route from the ER, and a large proportion of the carbohydrates it makes are attached as oligosaccharide side chains to the proteins and lipids that the ER sends to it. Certain oligosaccharide groups serve as tags to direct specific proteins into vesicles that will transport them to lysosomes; other proteins and lipids, once they have acquired their appropriate oligosaccharides in the Golgi apparatus, are dispatched in transport vesicles to other destinations.

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Receptors for the ER retention signal are also found in the cis, medial, and trans Golgi cisternae. Thus the retrieval of ER proteins begins in the cis Golgi network, but the return pathway operates from the later Golgi cisternae as well. The retention is aided by interactions between ER-resident proteins in the ER lumen. These interactions retard the exit of ER proteins relative to proteins that are destined for secretion The mechanism used to retain resident proteins in the ER. ER-resident proteins that escape to the cis Golgi network are returned to the ER by vesicular transport. A membrane receptor in the cis Golgi network aptures the proteins and carries them in transport vesicles back to the ER. The ionic conditions in the ER dissociate the ER proteins from the receptor, and the receptor is then returned to the cis Golgi network for reuse .

Transport from the Trans Golgi Network to Lysosomes:

Transport from the Trans Golgi Network to Lysosomes

Slide 66:

Lysosomes are membranous bags of hydrolytic enzymes used for the controlled intracellular digestion of macromolecules. They contain about 40 types of hydrolytic enzymes, including proteases, nucleases, glycosidases, lipases, phospholipases, phosphatases, and sulfatases. All are acid hydrolases. For optimal activity they require an acid environment, and the lysosome provides this by maintaining a pH of about 5 in its interior. In this way the contents of the cytosol are doubly protected against attack by the cell's own digestive system. The membrane of the lysosome normally keeps the digestive enzymes out of the cytosol, but even if they should leak out, they can do little damage at the cytosolic pH of about 7.2. Transport proteins in this membrane allow the final products of the digestion of macromolecules, such as amino acids, sugars, and nucleotides, to be transported to the cytosol, from where they can be either excreted or reutilized by the cell. An H + pump in the lysosomal membrane utilizes the energy of ATP hydrolysis to pump H + into the lysosome, thereby maintaining the lumen at its acidic pH (Figure 13-17). Most of the lysosomal membrane proteins are unusually highly glycosylated, which is thought to help protect them from the lysosomal proteases in the lumen.

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Lysosomes. The acid hydrolases are hydrolytic enzymes that are active under acidic conditions. The lumen is maintained at an acidic pH by an H + ATPase in the membrane that pumps H + into the lysosome.

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Three pathways to degradation in lysosomes. Each pathway leads to the intracellular digestion of materials derived from a different source. The compartments resulting from the three pathways can sometimes be distinguished morphologically - hence the terms "autophagolysosome," "phago-lysosome," and so on. Such lysosomes, however, may differ only because of the different materials they are digesting

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The routes that lead inward to lysosomes from the cell surface start with the process of endocytosis, by which cells take up macromolecules, particulate substances, and, in specialized cases, even other cells. Material to be ingested is progressively enclosed by a small portion of the plasma membrane, which first invaginates and then pinches off to form an intracellular vesicle containing the ingested substance or particle. Two main types of endocytosis are distinguished on the basis of the size of the endocytic vesicles formed: pinocytosis ("cellular drinking"), which involves the ingestion of fluid and solutes via small vesicles (£ 150 nm in diameter), and p hagocytosis ("cellular eating"), which involves the ingestion of large particles, such as microorganisms or cell debris, via large vesicles called phagosomes, generally > 250 nm in diameter. Although most eucaryotic cells are continually ingesting fluid and solutes by pinocytosis, large particles are ingested mainly by specialized phagocytic cells.

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A low-density lipoprotein (LDL) particle. Each spherical particle has a mass of 3 x 10 6 daltons. It contains a core of about 1500 cholesterol molecules esterified to long-chain fatty acids that is surrounded by a lipid monolayer composed of about 800 phospholipid and 500 unesterified cholesterol molecules. A single molecule of a 500,000-dalton protein organizes the particle and mediates the specific binding of LDL to cell-surface receptor proteins

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Normal and mutant LDL receptors. (A) LDL receptor proteins binding to a coated pit in the plasma membrane of a normal cell. The human LDL receptor is a single-pass transmembrane glycoprotein composed of about 840 amino acid residues, only 50 of which are Plasma Membrane on the cytoplasmic side of the membrane. (B) A mutant cell in which the LDL receptor proteins are abnormal and lack the site in the cytoplasmic domain that enables them to bind to coated pits. Such cells bind LDL but cannot ingest it. In most human populations 1 in 500 individuals inherits one defective LDL receptor gene and, as a result, is likely to die prematurely from a heart attack caused by atherosclerosis.

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For simplicity, only one LDL receptor is shown entering the cell and returning to the plasma membrane. Whether it is occupied or not, an LDL receptor typically makes one round trip into the cell and back to the plasma membrane every 10 minutes, making a total of several hundred trips in its 20-hour life-span. Receptor-mediated endocytosis of LDL. Note that the LDL dissociates from its receptors in the acidic environment of the endosome. After a number of steps the LDL ends up in lysosomes, where it is degraded to release free cholesterol. In contrast, the LDL receptor proteins are returned to the plasma membrane via transport vesicles that bud off from the tubular region of the endosome, as shown.

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Two distinct early endosomal compartments in an epithelial cell. The basolateral and the apical domain of the plasma membrane communicate with distinct early endosomal compartments, although endocytosed molecules from both domains that do not contain signals for recycling or transcytosis meet in a common late endosomal compartment before being digested in lysosomes.

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Transport from the Trans Golgi Network to the Cell Surface: Exocytosis

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The regulated and constitutive secretory pathways. The two pathways diverge in the trans Golgi network. Many soluble proteins are continually secreted from the cell by the constitutive secretory pathway (also called the default pathway ) , which operates in all cells. This pathway also supplies the plasma membrane with newly synthesized lipids and proteins. Specialized secretory cells also have a regulated secretory pathway, by which selected proteins in the trans Golgi network are diverted into secretory vesicles, where the proteins are concentrated and stored until an extracellular signal stimulates their secretion. The regulated secretion of small molecules, such as histamine, occurs by a similar pathway: these molecules are actively transported from the cytosol into preformed secretory vesicles. There they are often complexed to specific macro-molecules (proteoglycans in the case of histamine), so that they can be stored at high concentration without generating an excessively high osmotic pressure.