Comprehensive Physiology Wiley Online Library

Regulated Exocytosis in Mammalian Secretory Cells

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Entry of Proteins into the Secretory Pathway
1.1 Mechanism of Sorting of Membrane and Secretory Proteins into the Secretory Pathway
1.2 Mechanism of Movement of Secretory Vesicles to the Plasma Membrane and Endocytic Vesicles from the Plasma Membrane
2 Mechanisms of Membrane Interactions on the Secretory Pathway
2.1 The SNARE Hypothesis of Vesicular Targeting and Membrane Fusion
2.2 Control Proteins in Exocytosis
2.3 The Role of rab Proteins in Exocytosis and Endocytosis
3 Membrane Retrieval Following Regulated Exocytosis
Figure 1. Figure 1.

Schematic representation of polarized, regulated secretory cell indicating main steps involved in intracellular transport and exocytosis of secretory proteins. Note existence of at least three pathways of exocytosis: classic regulated exocytosis pathway, constitutive secretion from basolateral pole of cell, and constitutive‐like pathway from forming secretory granules to cell surface. RER, rough endoplasmic reticulum; TGN, trans Golgi network; ZG, zymogen granule; CV, condensing vacuole; GC, Golgi cisterna; LY, lysome; tr, transitional element.

Figure 2. Figure 2.

Diagram of early steps of regulated exocytosis prior to actual fusion step and exocytosis. Interaction of v‐ and t‐SNARE proteins in initial recognition and docking of secretory granules with apical plasmalemma is shown, as is parting of actin “clamp” that normally prevents spontaneous exocytosis. SNAP, soluble NSF attachment protein; SNARE, soluble NSF attachment protein receptor; v, transport vesicle; t, target membrane; VAMP, vesicle‐associated membrane proteins.

Figure 3. Figure 3.

Diagram of fate of secretory granule membrane proteins following insertion into plasmalemma that accompanies regulated exocytosis. Reorientation of synaptotagmin in plasma membrane and subsequent interaction with adaptor proteins and clathrin to form coated vesicles is suggested. GDI, guanosine diphosphate dissociation inhibitor.

Figure 4. Figure 4.

Schematic representation depicting membrane‐cytosol cycle of rab proteins. In GTP‐bound or “on” state, isoprenylated rab protein is associated with donor membrane compartment, illustrated here as secretory vesicle. Upon fusion of donor membrane with its target—that is, plasma membrane—rab protein hydrolyzes GTP into GDP and becomes cytosolic, forming a complex with rab‐GDI; rab protein is now in “off” state until it exchanges its GDP for GTP and becomes newly membrane associated. During cycle, rab proteins probably interact with other regulatory proteins such as rabphilin, GAP and GDS, but precise site of action is yet unclear, and they have therefore not been included in this model.



Figure 1.

Schematic representation of polarized, regulated secretory cell indicating main steps involved in intracellular transport and exocytosis of secretory proteins. Note existence of at least three pathways of exocytosis: classic regulated exocytosis pathway, constitutive secretion from basolateral pole of cell, and constitutive‐like pathway from forming secretory granules to cell surface. RER, rough endoplasmic reticulum; TGN, trans Golgi network; ZG, zymogen granule; CV, condensing vacuole; GC, Golgi cisterna; LY, lysome; tr, transitional element.



Figure 2.

Diagram of early steps of regulated exocytosis prior to actual fusion step and exocytosis. Interaction of v‐ and t‐SNARE proteins in initial recognition and docking of secretory granules with apical plasmalemma is shown, as is parting of actin “clamp” that normally prevents spontaneous exocytosis. SNAP, soluble NSF attachment protein; SNARE, soluble NSF attachment protein receptor; v, transport vesicle; t, target membrane; VAMP, vesicle‐associated membrane proteins.



Figure 3.

Diagram of fate of secretory granule membrane proteins following insertion into plasmalemma that accompanies regulated exocytosis. Reorientation of synaptotagmin in plasma membrane and subsequent interaction with adaptor proteins and clathrin to form coated vesicles is suggested. GDI, guanosine diphosphate dissociation inhibitor.



Figure 4.

Schematic representation depicting membrane‐cytosol cycle of rab proteins. In GTP‐bound or “on” state, isoprenylated rab protein is associated with donor membrane compartment, illustrated here as secretory vesicle. Upon fusion of donor membrane with its target—that is, plasma membrane—rab protein hydrolyzes GTP into GDP and becomes cytosolic, forming a complex with rab‐GDI; rab protein is now in “off” state until it exchanges its GDP for GTP and becomes newly membrane associated. During cycle, rab proteins probably interact with other regulatory proteins such as rabphilin, GAP and GDS, but precise site of action is yet unclear, and they have therefore not been included in this model.

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Dola Sengupta, Jack A. Valentijn, James D. Jamieson. Regulated Exocytosis in Mammalian Secretory Cells. Compr Physiol 2011, Supplement 31: Handbook of Physiology, Cell Physiology: 649-664. First published in print 1997. doi: 10.1002/cphy.cp140116