Molecular mechanisms of lacrimal acinar secretory vesicle exocytosis

Wu, Kaijin; Jerdeva, Galina V.; Costa, Silvia R. da; Sou, Eunbyul; Schechter, Joel; Hamm‐Alvarez, Sarah F.

doi:10.1016/j.exer.2005.11.009

Cited by 43 publications

(34 citation statements)

References 105 publications

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“…These defects ultimately result from the lack of VAMP8 that is important for fusion of secretory granules with the plasma membrane. VAMP2, VAMP7, and VAMP8 have been proposed to be candidate v-SNAREs in lacrimal glands (Wu et al, 2006). Our study shows that VAMP8 is a major if not the only v-SNARE of lacrimal glands.…”

Section: Discussionmentioning

confidence: 52%

VAMP8/Endobrevin as a General Vesicular SNARE for Regulated Exocytosis of the Exocrine System

Wang

Shi

Guo

et al. 2007

MBoC

100

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The molecular mechanism governing the regulated secretion of most exocrine tissues remains elusive, although VAMP8/ endobrevin has recently been shown to be the major vesicular SNARE (v-SNARE) of zymogen granules of pancreatic exocrine acinar cells. In this article, we have characterized the role of VAMP8 in the entire exocrine system. Immunohistochemical studies showed that VAMP8 is expressed in all examined exocrine tissues such as salivary glands, lacrimal (tear) glands, sweat glands, sebaceous glands, mammary glands, and the prostate. Severe anomalies were observed in the salivary and lacrimal glands of VAMP8-null mice. Mutant salivary glands accumulated amylase and carbonic anhydrase VI. Electron microscopy revealed an accumulation of secretory granules in the acinar cells of mutant parotid and lacrimal glands. Pilocarpine-stimulated secretion of saliva proteins was compromised in the absence of VAMP8. Protein aggregates were observed in mutant lacrimal glands. VAMP8 may interact with syntaxin 4 and SNAP-23. These results suggest that VAMP8 may act as a v-SNARE for regulated secretion of the entire exocrine system.

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Section: Discussionmentioning

confidence: 52%

VAMP8/Endobrevin as a General Vesicular SNARE for Regulated Exocytosis of the Exocrine System

Wang

Shi

Guo

et al. 2007

MBoC

100

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“…The direct link between the clinical manifestations of dry eye and the decreased secretory function of the LG suggest that fundamental studies on secretory mechanisms within the LG acinar cells are necessary for the development of better therapeutic strategies for treatment of dry eye (15,52). Although we focused mainly on the morphological changes in LG of 27bKO and DKO mice, preliminary studies characterizing DKO mice suggest that these mice exhibit alterations in tears that may be indicative of dry eye disease, although the mechanism is likely complex.…”

Section: Discussionmentioning

confidence: 99%

“…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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“…KIFC3 carries Annexin XIIIb apically-bound vesicles for constitutive exocytosis [58]. Minus-end directed kinesins and dyneins are also involved in apical secretion [59,60,61]. Therefore, the apical localization of the minus-ends of microtubules is expected to be functionally more important for apical exocytosis and secretion than the apico-basal architecture of the microtubular apparatus, that has been shown to be dispensable for apical polarization [46].…”

Section: Role Of Keratin Ifs In the Subcellular Localization Of Micromentioning

confidence: 99%

Intermediate filaments: A role in epithelial polarity

Oriolo

Wald

Palau

et al. 2007

Experimental Cell Research

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Intermediate filaments have long been considered mechanical components of the cell that provide resistance to deformation stress. Practical experimental problems, including insolubility, lack of good pharmacological antagonists, and the paucity of powerful genetic models, have handicapped the research of other functions. In single-layered epithelial cells, keratin intermediate filaments are cortical, either apically polarized or apico-lateral. This review analyzes phenotypes of genetic manipulations of simple epithelial cell keratins in mice and C. elegans that strongly suggest a role of keratins in apico-basal polarization and membrane traffic. Published evidence that intermediate filaments can act as scaffolds for proteins involved in membrane traffic and signaling is also discussed. Such a scaffolding function would generate a highly polarized compartment within the cytoplasm of simple epithelial cells. While in most cases mechanistic explanations for the keratinnull or overexpression phenotypes are still missing, it is hoped investigators will be encouraged to study these as yet poorly understood functions of intermediate filaments.

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Molecular mechanisms of lacrimal acinar secretory vesicle exocytosis

Cited by 43 publications

References 105 publications

VAMP8/Endobrevin as a General Vesicular SNARE for Regulated Exocytosis of the Exocrine System

VAMP8/Endobrevin as a General Vesicular SNARE for Regulated Exocytosis of the Exocrine System

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

Intermediate filaments: A role in epithelial polarity

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