β-granule transport and exocytosis

Easom, Richard A.

doi:10.1006/scdb.2000.0174

Cited by 75 publications

(67 citation statements)

References 143 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In neurons Cdk5 has been shown to phosphorylate numerous substrates and thereby modulating several different intracellular signaling cascades that may directly or indirectly influence secretion. For example, both in neurons and in ␤-cells the cytoskeleton is pivotal for membrane vesicle transport (50,55,56). Cdk5 is regarded as a neuron-specific Rac regulator causing hyperphosphorylation of the small GTPase Pak 1, and thereby modulating actin cytoskeleton dynamics (32).…”

Section: Discussionmentioning

confidence: 99%

Cyclin-dependent Kinase 5 Promotes Insulin Exocytosis

Lilja

Yang

Webb

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

Cyclin-dependent kinase 5 (Cdk5) is widely expressed although kinase activity has been described preferentially in neuronal systems. Cdk5 has an impact on actin polymerization during neuronal migration and neurite outgrowth and deregulation of the kinase has been implicated in the promotion of neurodegeneration. Recently it was shown that Cdk5 modulates dopamine signaling in neurons by regulating DARPP-32 function. In addition, Cdk5 phosphorylates munc-18 and synapsin I, two essential components of the exocytotic machinery. We have shown by reverse transcriptase-polymerase chain reaction, immunocytochemistry, and Western blotting that Cdk5 is present in the insulin-secreting pancreatic ␤-cell. Subcellular fractionation of isolated ␤-cells revealed a glucose-induced translocation of membrane-bound Cdk5 protein to lower density fractions. Inhibition of Cdk5 with roscovitine reduced insulin secretion with ϳ35% compared with control after glucose stimulation and with ϳ65% after depolarization with glucose and KCl. Capacitance measurements performed on single ␤-cells that expressed a dominantnegative Cdk5 mutant showed impaired exocytosis. The effect on exocytosis by Cdk5 appeared to be independent of changes in free cytoplasmic Ca 2؉ concentration. Taken together these results show that Cdk5 is present in ␤-cells and acts as a positive regulator of insulin exocytosis.Insulin is stored in secretory granules in pancreatic ␤-cells and upon stimulation with secretagogues insulin is released by exocytosis. Exocytosis has been suggested to be mediated by the same core fusion machinery that traverses intracellular membrane traffic in all cells (1-3). It was reported that the membrane fusion event required the N-ethylmaleimide sensitive factor (NSF), 1 and soluble NSF Attachment Proteins, ␣-, ␤-, and ␥-SNAP (1, 2). In addition to NSF and SNAPs, a 7 S core complex with SNAp receptors or "SNARE" proteins corresponding to the vesicle component synaptobrevin/vesicular-associated membrane protein, as well as the plasma membrane proteins SNAP-25 (synaptosomal-associated protein of 25 kDa) and syntaxin were necessary for neuronal exocytosis (3). The SNARE hypothesis proposes that the SNARE proteins form trans-complexes between adjacent membranes, thereby forcing them to proximity. After association of ␣-SNAP, the ATPase NSF completes the reaction by disassembling the SNARE complex leading to membrane bilayer mixing (3). More recently, trans-SNARE pairing and NSF activity has been suggested to act either prior to docking of vesicles or after membrane bilayer mixing (4 -9). Initially the SNARE proteins were regarded as neuron-specific. However, syntaxin, SNAP-25, synaptobrevin/ vesicular-associated membrane protein, and other synaptic proteins regulating neuronal exocytosis have also been identified in pancreatic ␤-cells, suggesting that the mechanism for insulin secretion is similar to that of neurotransmitter release from synaptic vesicles in neurons (10 -13). Regulated secretion of insulin from pancreatic ␤-cells has to be tightl...

show abstract

Section: Discussionmentioning

confidence: 99%

Cyclin-dependent Kinase 5 Promotes Insulin Exocytosis

Lilja

Yang

Webb

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…However, some components of the secretory machinery of pancreatic ␤-cells have been identified. These components include the SNAREs VAMP-2, SNAP25, and syntaxin-1a and different Rab GTPases (Lang, 1999;Easom, 2000). Rab GTPases constitute a large family of proteins (more than 60 members in humans) that govern intracellular vesicular trafficking in eukaryotic cells (Martinez and Goud, 1998;Zerial and McBride, 2001).…”

Section: Introductionmentioning

confidence: 99%

Involvement of the Rab27 Binding Protein Slac2c/MyRIP in Insulin Exocytosis

Waselle

Coppola

Fukuda

et al. 2003

MBoC

152

159

View full text Add to dashboard Cite

show abstract

“…Unfortunately, little is known about how increases in [Ca 2+ ] i evoke specific protein components of the -cell to interact for triggering insulin exocytosis (Wollheim et al 1996, Easom 2000. Analogies have been made to the mechanism of regulated synaptic vesicle exocytosis in neurons to help identify proteins that are necessary for the control of insulin exocytosis, and indeed there are similar protein isoforms involved (Burgoyne & Morgan 2003).…”

Section: Introductionmentioning

confidence: 99%

Intragranular targeting of syncollin, but not a syncollinGFP chimera, inhibits regulated insulin exocytosis in pancreatic β-cells

Hays¹,

Wicksteed²,

Y³

et al. 2005

Journal of Endocrinology

View full text Add to dashboard Cite

Several proteins play a role in the mechanism of insulin exocytosis. However, these 'exocytotic proteins' have yet to account for the regulated aspect of insulin exocytosis, and other factors are involved. In pancreatic exocrine cells, the intralumenal zymogen granule protein, syncollin, is required for efficient regulated exocytosis, but it is not known whether intragranular peptides similarly influence regulated insulin exocytosis. Here, this issue has been addressed using expression of syncollin and a syncollingreen fluorescent protein (syncollinGFP) chimera in rat islet -cells as experimental tools. Syncollin is not normally expressed in -cells but adenoviral-mediated expression of both syncollin and syncollinGFP indicated that these were specifically targeted to the lumen of -granules. Syncollin expression in isolated rat islets had no effect on basal insulin secretion but significantly inhibited regulated insulin secretion stimulated by glucose (16·7 mM), glucagon-like peptide-1 (GLP-1) (10 nM) and glyburide (5µM). Consistent with specific localization of syncollin to -granules, constitutive secretion was unchanged by syncollin expression in rat islets. Syncollin-mediated inhibition of insulin secretion was not due to inadequate insulin production. Moreover, secretagogue-induced increases in cytosolic intracellular Ca 2+, which is a prerequisite for triggering insulin exocytosis, were unaffected in syncollin-expressing islets. Therefore, syncollin was most likely acting downstream of secondary signals at the level of insulin exocytosis. Thus, syncollin expression in -cells has highlighted the importance of intralumenal -granule peptide factors playing a role in the control of insulin exocytosis. In contrast to syncollin, syncollinGFP had no effect on insulin secretion, underlining its usefulness as a 'fluorescent tag' to track -granule transport and exocytosis in real time.

show abstract

β-granule transport and exocytosis

Cited by 75 publications

References 143 publications

Cyclin-dependent Kinase 5 Promotes Insulin Exocytosis

Cyclin-dependent Kinase 5 Promotes Insulin Exocytosis

Involvement of the Rab27 Binding Protein Slac2c/MyRIP in Insulin Exocytosis

Intragranular targeting of syncollin, but not a syncollinGFP chimera, inhibits regulated insulin exocytosis in pancreatic β-cells

Contact Info

Product

Resources

About