Biological Sciences

Exocytosis and Endocytosis

Exocytosis is the process by which cells release molecules or waste materials by fusing vesicles with the cell membrane, allowing the contents to be expelled into the extracellular space. Endocytosis, on the other hand, involves the uptake of materials into the cell by the formation of vesicles from the cell membrane. Both processes are essential for maintaining cellular function and homeostasis.

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11 Key excerpts on "Exocytosis and Endocytosis"

  • Book cover image for: Mammalian Cell Membranes
    eBook - PDF

    Mammalian Cell Membranes

    Responses of Plasma Membranes

    In addition to the terms endo-and exocytosis (De Duve, 1963), they introduced the term intracytosis to describe intracellular processes of membrane vesiculation. In this chapter, a somewhat modified division of bulk transport will be given, similar to that of Bennett (1969b) and Jacques (1975). Bulk transport Permeation-Bulk transport (Diffusion, facilitated diffusion, active transport) Inward membrane perforation-Outward membrane perforation (Uptake of bacteriophage, etc.) (Excretion, etc.]_ Secretion Cellular budding Positive endocytosis-Negative endocytosis Positive intracytosis-Negative intracytosis Positive exocytosis-Negative exocytosis (Vacuole fusion, (Formation of Golgi cell plate forma- vesicles, secondary tion, formation of micropinocytosis, secondary lyso- formation of small _,, ■ . . somes, formation secondary endosomes) Phagocytos.s o f larg ' e sec ondary endosomes ) (Reverse cellular budding, cell fusion) Pinocytosis Potocytosis Granulopexy Rhopheocytosis Colloidopexy Ultraphagocytosis Chromopexy Ultramicrophagocytosis Phagotrophy Micropinocytosis Micellophagosis Athrocytosis Granulocytosis Dye storage Figure 6.1 Synopsis of the different mechanisms used by the cellfor the transport of substances. See Section 6.2 for explanation 155 154 ENDOGYTOSIS by membrane perforation can be accepted in the form defined by Jacques, provided one distinguishes between inward and outward transport. Under inward membrane perforation one can include processes, such as the uptake of bacteriophages, through which extracellular particles are directly trans-ported into the cytoplasmic matrix by means of an opening made for a short time in the cell membrane (Figure 6.2a-c, 1). Outward membrane perforation has been suggested by Hausmann and Stockem (1972) and Stockem (1972) for defecation* in amebae (cf. Figure 6.2e-g, 8, and Figure 6.21, p. 186).
  • Book cover image for: Single-Molecule Cellular Biophysics
    Exocytosis can be viewed in a naı ¨ve way as the reverse of this in that it involves the expulsion of molecules from the cell membrane via secretory vesicles. However, the molecular modes of action of each are distinct, and both have been studied in live, functional cells using single-molecule techniques. Cargo sorting of large molecules can be mediated by a process which is very similar to the mechanism of A C D 1.3 kcounts 1s 0 10 0 50 100 ~34 molecules 20 30 E FliM-YPet (molecules per foci) 0 50 100 Frequency of spots (%) ~1.3 kcounts ~22 ~34 5 10 15 0 B 10 kcounts 1s F Normalised power 0 1 Intensity (kcounts) 0 1 2 3 ~12 FIGURE 7.3 Using step-wise photobleaching to estimate FliM-YPet stoichiometry. (A) Sequential TIRF images of live cells plus overlaid brightfield images for a tethered, rotating FliM-YPet cell; the motor is at the centre of rotation, the direction of rotation is indicated (arrow). (B) Corresponding photobleach fluorescence intensity trace for a motor showing raw (dots) and filtered (line) motor intensity with (C) expansion of trace (grid lines at intervals of a single YPet molecule intensity, in this case each consisting of ~1300 counts on the camera detector used in the microscope), and (D) Fourier spectral analysis predicting the brightness of a single YPet molecule. Stoichiometry distributions for (E) tethered and (F) immobilized cells, peaks indicated (arrows). (For full details see Delalez et al., 2010.) 168 Molecules from beyond the cell endocytosis, which we also encounter briefly here but return to subsequently in Chapter 9 when discussing how cargoes are trafficked specifically in the cell using molecular motors. 7.3.1 Live-cell imaging of clathrin-based endocytosis Relatively large molecules such as proteins in general have some net electrostatic polarity and so will encounter a very large free energy barrier when crossing the cell membrane from the outside of the cell to the inside (see Chapter 2).
  • Book cover image for: Crosstalk and Integration of Membrane Trafficking Pathways
    • Roberto Weigert(Author)
    • 2012(Publication Date)
    • IntechOpen
      (Publisher)
    7 Endocytosis and Exocytosis in Signal Transduction and in Cell Migration Guido Serini 1,2 , Sara Sigismund 3 and Letizia Lanzetti 2,4 1 Cell Adhesion Dynamics Laboratory-IRCC, Candiolo 2 Department of Oncological Sciences University of Torino 3 1IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan 4 Membrane Trafficking Laboratory- IRCC, Candiolo Italy 1. Introduction Endocytosis is a complex process that is used by eukaryotic cells to internalize fragments of plasma membrane, cell-surface receptors, and various soluble molecules. Many different mechanisms have been developed to achieve internalization of membrane-bound receptors and their ligands and they can be distinguished in clathrin-mediated endocytosis and non-clathrin internalization routes. In the clathrin-mediated endocytosis, receptors bind to the adaptor protein AP2 that, in turn, recruits clathrin to coat the invaginating pits at the plasma membrane. Coated pits are pinched off by the large GTPase dynamin to generate vesicles that traffic from the plasma membrane, undergo uncoating and fuse to the early endosomal compartment. Of note, dynamin is also required in non-clathrin-mediated endocytosis [for detailed recent reviews see (Doherty & McMahon, 2009; Loerke et al, 2009; Mettlen et al, 2009; Traub, 2009)]. From early endosomes vesicles can be re-delivered to the plasma membrane through the exocytic pathway (Grant & Donaldson, 2009). Vesicle budding, uncoating, motility and fusion are controlled by the large family of Rab small GTPases. Rab proteins, in their active GTP-bound form, recruit downstream effectors that, in turn, are responsible for distinct aspects of endosomes function from signal transduction to selection and transport of cargoes. Furthermore, they control vesicular movements on microtubules thus supporting polarized distribution of internalized receptors and signalling molecules [reviewed in (Stenmark, 2009; Zerial & McBride, 2001)].
  • Book cover image for: Structure and Properties of Cell Membrane Structure and Properties of Cell Membranes
    • Gheorghe Benga, Benga(Authors)
    • 2018(Publication Date)
    • CRC Press
      (Publisher)
    FIGURE 1. Diagrammatic representation of Exocytosis and Endocytosis.Uptake of large particles by phagocytosis, including receptor mediated via coated vesicles, and uptake of fluids and solutes by pinocytosis are depicted as pathways separate and distinct but interacting with the biosynthetic and secretory pathways of exocytosis to the cell’s exterior.
    The passage of secretory materials through the Golgi apparatus has been amply demonstrated by electron microscope autoradiography using tritiated precursors as labels.1 , 19 , 20 , 21 , 22 , 23 , 24 As examples, for the guinea pig pancreas21 and the rabbit parotid gland23 following a 3- to 5min pulse label with [3 H] amino acid, the half-time for exit of labeled secretory proteins from the rough endoplasmic reticulum is 7 to 22 min and the half-time of entry into mature granules is greater than 60 min (Figure 4 ).
    However, Golgi apparatus activities associated with packaging and secretion may extend beyond those of segregation, processing, and sorting. Certain marine algae carry out a complex process of stepwise assembly and secretion of complex wall units known as scales entirely within the cisternae of the Golgi apparatus.25 , 26 In Pleurochrysis scherffeli, the completed cellulosic scales are discharged at a rate of one about every 2 min, each scale surrounded completely by the membrane of a single Golgi apparatus cisterna. The process has been viewed and recorded in living cells,27 on the one hand, to provide an opportunity to monitor precisely the kinetics of cisternal formation and discharge by Golgi apparatus.28 Additionally, from a knowledge of the complex architecture of the scales,26
  • Book cover image for: Extracellular Vesicles and Their Importance in Human Health
    • Ana Gil De Bona, Jose Antonio Reales Calderon, Ana Gil De Bona, Jose Antonio Reales Calderon(Authors)
    • 2020(Publication Date)
    • IntechOpen
      (Publisher)
    The methods by which exosomes influence the cells with which they interact are still under review. Some exosomes have been shown to fuse to the recipient cell [15, 16], while others are internalized by specific receptor-ligand interactions [17, 18] or by stimulating an indirect uptake by macropinocytosis [19]. Exosome binding to cells has been seen both as a mechanism of transferring luminal contents [15, 16] and as an initial step in the endocytosis process [17, 20]. The significance of the effects of cell-exosome binding in comparison to internalization is still unknown. Most types of endocytosis have been described in the process of exosome uptake [21], but which factors determine the specific mechanism used, are still unclear. Previous reviews have clearly identified a number of ligands and receptors involved in exosome trafficking [21–23], but little is known about the dependence of uptake mechanism on cell-type. This review presents the current understanding of the endocytosis process utilized by specific cells involved in exosomal internalization. 2. Endocytosis pathways Endocytosis is a basic cellular function that is performed by all cell types in the process of maintaining homeostasis. Many of the molecules essential for cellular function are small enough to cross the cell membrane either passively or actively, however, other structures, such as exosomes, are too large and require a more complicated process. This general process of internalization is called endocytosis and is separated into various types based on the shape [24] and the size of particles internalized [25]. There are many well-written reviews covering the specifics of the endocytic pathways [25, 26], but here we will address them only superficially.
  • Book cover image for: Extracellular Vesicles in Health and Disease
    • Paul Harrison, Chris Gardiner, Ian L. Sargent, Paul Harrison, Chris Gardiner, Ian L. Sargent(Authors)
    • 2014(Publication Date)
    The reason why this is such a dif ficult task lies in the incomplete knowledge on their biogenesis and secretion, thus precluding specific blockage or induction of exosome secretion in specific cell types or conditions in vivo . 2.1.3 Exosomes as an Alternative End of the Endosomal Pathway Exosomes are classically defined as vesicles that are derived from late endosomes (LEs). LEs are recognized as highly dynamic and heterogeneous structural compartments in eukaryotic cells. The endosomal membranes serve as major sorting platforms for molecules that have been taken up and internalized by invaginations at the plasma membrane. Collectively this process is known as endocytosis, and the endosomal system thus represents a key direct contact of the cell with its exterior apart from the plasma membrane. Endocytosis starts with the internalization of fluid, solutes, mac-romolecules, plasma membrane components, and particles through various pathways of endocytic traf ficking. 56 Not surprisingly, the en-docytic pathway is heavily exploited by viruses and other intracellu-lar parasites that wish to gain entry into specific host cells to support their life cycle. A functioning endosomal system is essential for nor-mal development and physiology, and impaired endosomal function contributes to many human diseases, including cancer, 57 neurologi-cal diseases, and immune disorders. 58–61 Endocytosed material from the plasma membrane is deposited via small transport vesicles into the early endosomes, also known as sorting endosomes. The early endosomes receive their cargo via multiple mechanisms, the clath- 53 rin- or non-clathrin-mediated pathways. The non-clathrin-depend-ent pathways are caveolar, GEEC- (GPI-enriched endocytic compart-ments) and ARF6-mediated. 62 Genetic studies in yeast identified a crucial, evolutionary, conserved molecular constituent of the endosomal compartments, most notably, the endosomal sorting complex required for transport (ESCRT) machinery.
  • Book cover image for: Protein Targeting
    • Anthony Pubsley(Author)
    • 2012(Publication Date)
    • Academic Press
      (Publisher)
    CHAPTER VIII Endocytosis Eukaryotic cells of many different types internalize a variety of proteins and other macromolecules from the surrounding environment and from the cell surface. In most but not all cases, internalization occurs via endocytosis, a process involving the invagination of specific regions of the plasma membrane to form vesicles which then migrate into the cytoplasm and away from the plasma membrane. Endocytosis is known or has been proposed to play an essential role in several aspects of cell physiology. (i) Nutrient uptake: many micronutrients are accumulated by endocy-tosis. Among the best characterized examples is iron, which is internalized as a complex with its specific binding protein, transfer-rin, from which iron is subsequently released in an internal com-partment (see Section VIII.A.5.a). (ii) The clearance of unwanted molecules from the blood stream by macrophages and hepatocytes: The endocytosed molecules are targeted to the lysosome, where they are degraded. (iii) The transcytosis of secretory class (IgA) and maternal (IgG) im-munoglobulins by epithelial cells (iv) The capture of 4 'escaped lysosomal proteins (v) Antigen processing and presentation (vi) The control of cell dimensions involving the recycling of plasma membrane material into late stages of the secretory pathway (vii) Pseudopodal locomotion (viii) The control of cell growth and development by growth factors and hormones (ix) DNA uptake by transformation In addition, many viruses, bacteria, and toxins fortuitously gain entry into eukaryotic cells by processes which are similar if not identical to endocy-tosis. 211 212 VIII. ENDOCYTOSIS Indeed, two different but probably convergent endocytic pathways can be distinguished by the requirement for a cell surface receptor for endocy-tosis.
  • Book cover image for: Nanoparticles in the Lung
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    Nanoparticles in the Lung

    Environmental Exposure and Drug Delivery

    • Akira Tsuda, Peter Gehr, Akira Tsuda, Peter Gehr(Authors)
    • 2014(Publication Date)
    • CRC Press
      (Publisher)
    • Endosomes are membrane-bound compartments (i.e., vesicles) inside eukary-otic cells. There is an intracellular trafficking from primary endocytotic vesicles toward late endosomes and finally lysosomes. • Lysosomes contain hydrolytic enzymes involved in intracellular digestions. • Peroxisomes contain oxidative enzymes that break down hydrogen peroxide, which is a by-product of cell metabolism. • Vacuoles are essentially storage units. 151 Cellular Uptake and Intracellular Trafficking 9.5 Exocytosis and Endocytosis of Macromolecules and Particles Most cells can secrete and ingest macromolecules and particles by Exocytosis and Endocytosis (Alberts et al . 1998). The plasma membrane of the cells is a dynamic structure and segregates the chemically distinct intracellular milieu (the cytoplasm) from the extracellular environ-ment by coordinating the entry and exit of small and large molecules. Figure 9.2 summa-rizes different possible cellular entering and intracellular trafficking mechanisms of NPs. It is important to note that viruses can take advantage of endocytotic pathways to enter host cells (for a review, see Barrow et al . 2013), and that this knowledge can be used for the development of new NP platforms for drug or vaccine delivery (Plummer and Manchester 2013). 9.6 Endocytosis While essentially small molecules are able to traverse the plasma membrane through the action of integral membrane protein pumps or channels, macromolecules must be carried 1 2 3 4 Nucleus 5 6 FIGURE 9.2 Possible mechanisms for NPs to be taken up by cells and their subsequent intracellular trafficking. NPs may be actively incorporated via phagocytosis (1), macropinocytosis (2), clathrin-dependent endocytosis (3), clathrin- and caveolae-independent endocytosis (4), or caveolae-mediated endocytosis (5). Particles that were internalized via active uptake are commonly transported via vesicular structures that then fuse to phagolysosomes or endo-somes (1 through 5).
  • Book cover image for: Principles of Medical Physiology, 2/E
    • Sabyasachi Sircar(Author)
    • 2016(Publication Date)
    • Thieme
      (Publisher)
    Depending on what is endocytosed, endocyto- sis is called phagocytosis or pinocytosis. Endocy- tosis of cells, bacteria, viruses, or debris is called phagocytosis. Endocytic vesicles containing these fuse with primary lysosomes to form second- ary lysosomes where the ingested particles are digested. Endocytosis of water, nutrient mol- ecules, and parts of the cell membrane is called pinocytosis. K + Na + Glucose Glucose Glucose GLUT-2 (glucose transporter) SGLT-1 (Na + -dependent glucose transporter) Passive uniport Secondary active symport Active antiport Na + –K + ATPase Fig. 5.6 Passive, active, and secondary active transport. SGLT-1 transports glucose against its concentration gra- dient. The energy for this uphill transport is derived from the favorable concentration gradient of Na + with which it is cotransported. The Na + concentration gradient is cre- ated by Na + –K + ATPase. Fig. 5.7 Chemical kinetics of simple diffusion and carrier- mediated membrane transport. Note that while the amount of carrier-mediated transport plateaus off at high solute concentration, there is no such limit to simple diffusion. V max K m Solute concentration Rate of transport 100% 50% 0 Simple diffusion C arrier m ediated General Physiology 40 Fluid-phase pinocytosis is a nonselective process in which the cell takes up fluid and all its solutes indiscriminately. Vigorous fluid-phase pinocyto- sis is associated with internalization of consider- able amounts of the plasma membrane. To avoid reduction in the surface area of the membrane, the membrane is replaced simultaneously by exocyto- sis of vesicles. In this way, the plasma membrane is constantly recycled. Absorptive pinocytosis is also called receptor- mediated pinocytosis. It is responsible for the up- take of selected macromolecules for which the cell membrane bears specific receptors. Such uptake minimizes the indiscriminate uptake of fluid or other soluble macromolecules.
  • Book cover image for: Biochemical Actions of Hormones V5
    2. Regulation of Exocytosis 59 The rate of intracellular transport of the secretory proteins through the various stages is influenced by prior stimulation. Bieger et al. (1976a,b) found that infusion of caerulin in vivo for 24 hours increased the intracellular transport of secretory proteins up to ten times the transport rate normally observed. E. DISCHARGE Secretory granules discharge their content by fusion with the plasma membrane followed by membrane fission of the fused membranes. As a result, the intragranular compartment becomes continuous with the ex-tracellular compartment. This process assures that the release of the se-cretory products is accomplished without disrupting the barrier between the cytosol and the extracellular space. F. MEMBRANE RETRIEVAL It is obvious that continued addition of secretory granule membrane to the plasma membrane would result in tremendous enlargement of the cell. Con-sequently, some mechanism must exist to retrieve or remove membrane from the plasma membrane in order to maintain a constant cell size. This topic will be taken up again in Section V. This short outline was intended to convey an idea of the overall processing of secretory proteins and some of its complexities. Subsequent portions of this article will deal primarily with topics that are relevant to stages D-F (Fig. 1). III. POSSIBLE MECHANISMS OF CELL MEMBRANE FUSION Because fusion between the plasmalemma and secretory granule mem-brane is a step fundamental to exocytosis, some of the general aspects of membrane fusion will be summarized. Poste and Allison (1973) have suggested that aggregation of intramem-branous particles is an important step in membrane fusion. In support of this notion, several chemical agents (dimethylsulfoxide, glycerol, and the ionophore A-23187) which caused cell fusion also caused aggregation of in-tramembranous particles as revealed by freeze-fracture (Mclntyre et al., 1974; Pinto da Silva and Martinez-Palomo, 1974; Vos et al, 1976).
  • Book cover image for: The Aspergilli
    eBook - PDF

    The Aspergilli

    Genomics, Medical Aspects, Biotechnology, and Research Methods

    • Gustavo H. Goldman, Stephen A. Osmani(Authors)
    • 2007(Publication Date)
    • CRC Press
      (Publisher)
    1 By mediating the down-regulation of plasma membrane receptors, endocytosis crucially regulates signal transduction, as illustrated by the carcinogenic effect of mutations in metazoan receptor tyrosine kinases that interferes with their ligand-induced internalization and subsequent lysosomal degradation, thus leading to their permanent signaling 2–4 or by the antiproliferative effect of mutations impairing the ligand-induced endocytic down-regulation of the G-protein coupled (GPCR) Saccharomyces cerevisiae Ste2p pheromone receptor that results in the inability of mutant yeasts to recover normally from a pheromone-induced cell cycle arrest. 5 A further example of involvement of endocytosis in fungal 178 The Aspergilli signal transduction is the essential role of the PalF arrestin in pH. 6 When coupled to exocytosis, endocytic recycling creates polarity, as demonstrated with the S. cerevisiae v-SNARE Snc1 in shmoo tips. 7 Recy-cling endosomes ensure delivery of chitin synthase III, a key cell wall biosynthetic enzyme, to polarized sites of growth. 8 In cells having highly active polarized secretions such as neurons, endocytosis is required for the efficient retrieval of the excess of membrane lipids and proteins (e.g., the aforementioned v-SNARE, denoted as synaptobrevin in neurons) delivered with synaptic vesicles, from the apical plasma membrane. Filamentous fungal hyphae contain an apical subcellular structure denoted as the Spitzenkörper (Spk), which involves a markedly high concentration of vesicles, 9 whose almost certain secretory origin is strongly suggested by its labeling with FM4-64 10 possibly through endocytic membrane recycling. Thus, the highly active localized exocytosis in hyphae poses a similar problem to that of the presynaptic terminal. Endocytosis plays a role in determining the lipid composition of the plasma membrane. Lipid rafts 11 form in the plasma membrane of metazoa and fungi. In yeast, these rafts are ergosterol- and ceramide-rich.
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