Comprehensive Physiology Wiley Online Library

Cell Biology of Secretion

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Intracellular Transport in Vesicles
2 Membrane Fusion and Exocytosis
2.1 Investigations in Synaptic Vesicles
2.2 Investigations in Yeast
2.3 Reconstituted Systems of Transport
2.4 Convergence of Separate Approaches
2.5 Calcium Dependence of Stimulated Neurotransmitter Release
2.6 Docking Vesicles to the Correct Membrane
2.7 Other Fusion Mechanisms
2.8 Evidence for SNAP‐NSF‐Mediated Docking/Fusion With Dense Core Granules
2.9 Exocytosis in Endocrine Cells
3 Membrane Budding and Endocytosis
3.1 Budding Involving Clathrin
3.2 Budding Involving COPI/ARF
3.3 Endocytosis in Endocrine Cells
3.4 Formation of Secretory Granules in Endocrine Cells
Figure 1. Figure 1.

Transport among membrane‐enclosed compartments in the cell. Proteins, after synthesis and transport into endoplasmic reticulum, undergo various sorting and processing procedures, and are transported through various compartments. In most cases, soluble proteins are only transported forward, but there is retrograde transport to return membrane components, including membrane proteins that belong in a previous compartment. Membrane and membrane proteins that arrive at the cell surface by constitutive or regulated secretion are returned by endocytosis to endosomes.

Figure 2. Figure 2.

Vesicular transport between compartments. Transport between the compartments, shown in Figure 1, is mediated through small membrane‐bound vesicles that bud off one compartment, diffuse to the next, and fuse with that compartment. In the example shown, the vesicle is transporting soluble proteins (cirdes) and membrane receptors (⋌). Transport in the opposite direction occurs through similar vesicles

Figure 3. Figure 3.

Possible sequence of steps in exocytosis in endocrine cells. Endocrine secretory granules approach the plasma membrane; synaptobrevin on the secretory granule membrane forms a complex with syntaxin and SNAP‐25 on the plasma membrane; this complex ensures the vesicle is docking to the correct membrane. These three proteins form a 7S complex in solution. When these three proteins, and possibly more not yet identified, have formed a complex, NSF and α‐SNAP bind, to form a larger 20S complex, followed by ATP hydrolysis. At this point, ATP is no longer required, so other steps that require ATP for priming are also complete. Several stages after ATP hydrolysis can be distinguished on the basis of temperature sensitivity (S3 to S2), pH sensitivity (S2 to S1, and response to Ca2 + (S1 to S*), which finally leads to release. [Taken from Parsons et al. 139, with permission.]

Figure 4. Figure 4.

Representation of a portion of the Golgi ribbon of a prolactin cell, developed from three dimensional electron microscopy. Prolactin is made on the endoplasmic reticulum (ER), and transported to the cis‐Golgi (cis‐element, CE). The Golgi ribbon is not continuous in the early section; there are gaps (wells, W) with small vesicles near these wells. The Golgi cisternae or saccules (S) and secretory granules are shown in cross section and the trans‐Golgi region and secretory granules again in three dimensions. Large aggregates of prolactin are seen in the trans‐Golgi region, which becomes progressively less solid. As the layer vesiculates, prolactin dense cores that have not yet separated merge to form larger cores. Budding of smaller vesicles, many with bristle coats, likely clathrin, continues until the large secretory granules are no longer attached to the layer. [Taken from Rambourg et al. 153 with permission.]



Figure 1.

Transport among membrane‐enclosed compartments in the cell. Proteins, after synthesis and transport into endoplasmic reticulum, undergo various sorting and processing procedures, and are transported through various compartments. In most cases, soluble proteins are only transported forward, but there is retrograde transport to return membrane components, including membrane proteins that belong in a previous compartment. Membrane and membrane proteins that arrive at the cell surface by constitutive or regulated secretion are returned by endocytosis to endosomes.



Figure 2.

Vesicular transport between compartments. Transport between the compartments, shown in Figure 1, is mediated through small membrane‐bound vesicles that bud off one compartment, diffuse to the next, and fuse with that compartment. In the example shown, the vesicle is transporting soluble proteins (cirdes) and membrane receptors (⋌). Transport in the opposite direction occurs through similar vesicles



Figure 3.

Possible sequence of steps in exocytosis in endocrine cells. Endocrine secretory granules approach the plasma membrane; synaptobrevin on the secretory granule membrane forms a complex with syntaxin and SNAP‐25 on the plasma membrane; this complex ensures the vesicle is docking to the correct membrane. These three proteins form a 7S complex in solution. When these three proteins, and possibly more not yet identified, have formed a complex, NSF and α‐SNAP bind, to form a larger 20S complex, followed by ATP hydrolysis. At this point, ATP is no longer required, so other steps that require ATP for priming are also complete. Several stages after ATP hydrolysis can be distinguished on the basis of temperature sensitivity (S3 to S2), pH sensitivity (S2 to S1, and response to Ca2 + (S1 to S*), which finally leads to release. [Taken from Parsons et al. 139, with permission.]



Figure 4.

Representation of a portion of the Golgi ribbon of a prolactin cell, developed from three dimensional electron microscopy. Prolactin is made on the endoplasmic reticulum (ER), and transported to the cis‐Golgi (cis‐element, CE). The Golgi ribbon is not continuous in the early section; there are gaps (wells, W) with small vesicles near these wells. The Golgi cisternae or saccules (S) and secretory granules are shown in cross section and the trans‐Golgi region and secretory granules again in three dimensions. Large aggregates of prolactin are seen in the trans‐Golgi region, which becomes progressively less solid. As the layer vesiculates, prolactin dense cores that have not yet separated merge to form larger cores. Budding of smaller vesicles, many with bristle coats, likely clathrin, continues until the large secretory granules are no longer attached to the layer. [Taken from Rambourg et al. 153 with permission.]

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Priscilla S. Dannies. Cell Biology of Secretion. Compr Physiol 2011, Supplement 20: Handbook of Physiology, The Endocrine System, Cellular Endocrinology: 3-22. First published in print 1998. doi: 10.1002/cphy.cp070101