Actin coating of secretory granules during regulated exocytosis correlates with the release of rab3D

Valentijn, Jack A.; Valentijn, Karine M.; Pastore, Lisa M.; Jamieson, James D.

doi:10.1073/pnas.97.3.1091

Cited by 127 publications

(119 citation statements)

References 33 publications

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“…Rab proteins, in particular Rab3, have been postulated to play a role in regulated exocytosis in the pancreatic acinar cell (34,46,47) and can potentially interact with acinar SNARE proteins (18). Jamieson et al have recently reported that Rab3 is required for actin coating of the apical ZGs (46). Whereas more work is needed to identify additional regulatory proteins involved in apical exocytosis, we have gained further insights into a regulator, Munc18c, that we believed to be involved in basolateral exocytosis.…”

Section: Discussionmentioning

confidence: 99%

Supramaximal cholecystokinin displaces Munc18c from the pancreatic acinar basal surface, redirecting apical exocytosis to the basal membrane

Gaisano¹,

Lutz²,

Leser³

et al. 2001

J. Clin. Invest.

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Section: Discussionmentioning

confidence: 99%

Supramaximal cholecystokinin displaces Munc18c from the pancreatic acinar basal surface, redirecting apical exocytosis to the basal membrane

Gaisano¹,

Lutz²,

Leser³

et al. 2001

J. Clin. Invest.

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“…Mature LG acinar cell SV localize beneath an actin-rich network underlying the APM; on stimulation, SV appear to undergo compound fusion followed by exocytosis of their contents at the APM (25). Myosin motors and actin filaments are believed to facilitate terminal aspects of SV fusion with APM and content extrusion; studies in LG acinar cells have collectively suggested that stimulation with the muscarinic agonist, carbachol (CCH), results in transient disassembly of the actin barrier beneath the APM concurrent with the assembly of actin "coats," which aid in the compound fusion of SV homotypically and with the APM (24,46,52). Both the unconventional myosin motor, myosin 5C, and non-muscle myosin II are thought to participate in aspects of terminal SV fusion (24,29).…”

mentioning

confidence: 99%

Rab27b regulates exocytosis of secretory vesicles in acinar epithelial cells from the lacrimal gland

Chiang¹,

Ngo²,

Schechter

et al. 2011

American Journal of Physiology-Cell Physiology

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mechanisms largely yet uncharacterized. We investigated the role of Rab27b in the terminal release of these secretory vesicles. Confocal fluorescence microscopy analysis of primary cultured rabbit lacrimal gland acinar cells revealed that Rab27b was enriched on the membrane of large subapical vesicles that were significantly colocalized with Rab3D and Myosin 5C. Stimulation of cultured acinar cells with the secretagogue carbachol resulted in apical fusion of these secretory vesicles with the plasma membrane. Evaluation of morphological changes by transmission electron microscopy of lacrimal glands from Rab27b Ϫ/Ϫ and Rab27 ash/ash /Rab27b Ϫ/Ϫ mice, but not ashen mice deficient in Rab27a, showed changes in abundance and organization of secretory vesicles, further confirming a role for this protein in secretory vesicle exocytosis. Glands lacking Rab27b also showed increased lysosomes, damaged mitochondria, and autophagosomelike organelles. In vitro, expression of constitutively active Rab27b increased the average size but retained the subapical distribution of Rab27b-enriched secretory vesicles, whereas dominant-negative Rab27b redistributed this protein from membrane to the cytoplasm. Functional studies measuring release of a cotransduced secretory protein, syncollin-GFP, showed that constitutively active Rab27b enhanced, whereas dominant-negative Rab27b suppressed, stimulated release. Disruption of actin filaments inhibited vesicle fusion to the apical membrane but did not disrupt homotypic fusion. These data show that Rab27b participates in aspects of lacrimal gland acinar cell secretory vesicle formation and release. actin; Rab3d; exocrine secretion; syncollin; mouse models A FUNCTIONING LACRIMAL GLAND (LG) is critical for a healthy ocular surface. This exocrine gland is the primary source of tear proteins and fluid, which, released up on the gland's exposure to sympathetic or parasympathetic agonists provided by innervating nerves, contribute to the middle aqueous layer of the precorneal film. Much of the LG's secretions originate from acinar cells, which constitute over 80% of the mass of the LG (13). These LG acinar cells produce a diverse array of secretory proteins that are internally sorted into large pools of serous and mucous secretory vesicles (SV) sized ϳ1 m in diameter and stored beneath the apical plasma membrane (APM) in preparation for regulated exocytosis. SV contents include nutrients and growth factors (lacritin and EGF), antibacterial and antiviral factors (secretory IgA and lactoferrin), and an array of proteases and lysosomal hydrolases (10, 39, 47). Despite its physiological importance, however, few studies have focused on the mechanisms of secretory membrane trafficking in LG acinar cells, in part due to the fragility and heterogeneity of these LG acinar SV relative to those in other acinar secretory cells, e.g., pancreatic acini (7).The current schematic of exocytosis in the LG acinar cell suggests multiple participants. Mature LG acinar cell SV localize beneath an actin-rich network und...

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“…Although this F-actin coat is thought to constitute a barrier to exocytosis (4 -7), secretory granules undergo exocytosis selectively at the apical membrane (8 -10). Redistribution of F-actin is induced during intense secretory activity (4,11,12), but it has remained unknown how F-actin regulates exocytosis in exocrine cells.…”

mentioning

confidence: 99%

Stabilization of Exocytosis by Dynamic F-actin Coating of Zymogen Granules in Pancreatic Acini

Nemoto

Kojima

Oshima

et al. 2004

Journal of Biological Chemistry

129

164

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Reorganization of F-actin in the apical region of mouse pancreatic acinar cells during Ca 2؉ -dependent exocytosis of zymogen granules was investigated by two-photon excitation microscopy with intact acini. Granules were rapidly coated with F-actin in response to either agonist stimulation or photolysis of a cagedCa 2؉ compound. Such F-actin coating occurred exclusively at the surface of granules undergoing exocytosis and was prevented either by latrunculin-A, which inhibits actin polymerization, or by Clostridium botulinum exoenzyme C3, which inhibits the small GTPase Rho. Latrunculin-A or exoenzyme C3 also triggered the formation of vacuoles in acinar cells, a characteristic of acute pancreatitis. Stimulation of acini with high concentrations of cholecystokinin, which cause acute pancreatitis in mice, also impaired the F-actin coating of granules and induced vacuole formation. Latrunculin-A reduced the latency to exocytosis but did not affect the total number of exocytic events, suggesting that F-actin slows and further stabilizes exocytosis by facilitating F-actin coating. Rho-dependent F-actin coating of granule membranes thus stabilizes exocytic structures and is necessary for physiological progression of sequetial compound exocytosis in the exocrine pancreas and for prevention of acute pancreatitis.

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Actin coating of secretory granules during regulated exocytosis correlates with the release of rab3D

Cited by 127 publications

References 33 publications

Supramaximal cholecystokinin displaces Munc18c from the pancreatic acinar basal surface, redirecting apical exocytosis to the basal membrane

Supramaximal cholecystokinin displaces Munc18c from the pancreatic acinar basal surface, redirecting apical exocytosis to the basal membrane

Rab27b regulates exocytosis of secretory vesicles in acinar epithelial cells from the lacrimal gland

Stabilization of Exocytosis by Dynamic F-actin Coating of Zymogen Granules in Pancreatic Acini

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