Ca2+-dependent Dephosphorylation of Kinesin Heavy Chain on β-Granules in Pancreatic β-Cells

Donelan, Matthew J.; Morfini, Gerardo; Julyan, Richard; Sommers, Scott; Hays, Lori B.; Kajio, Hiroshi; Briaud, Isabelle; Easom, Richard A.; Molkentin, Jeffery D.; Brady, Scott T.; Rhodes, Christopher J.

doi:10.1074/jbc.m203345200

Cited by 92 publications

(52 citation statements)

References 60 publications

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“…The BM secretagogue mixture (glucose, isobutylmethylxanthine, and KCl) is a very potent simulator of both first and second phase insulin secretion in Min6B1 cells (29). As expected, the combination of secretagogues in the BM mixture induced a striking increase in the rate of insulin secretion with an approximate 15-fold stimulation (Fig.…”

Section: Integral Membrane Proteins In Insulin Granules Do Notmentioning

confidence: 60%

Dynamin Is Functionally Coupled to Insulin Granule Exocytosis

Min

Leung

Tomás³

et al. 2007

Journal of Biological Chemistry

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The insulin granule integral membrane protein marker phogrin-green fluorescent protein was co-localized with insulin in Min6B1 ␤-cell secretory granules but did not undergo plasma membrane translocation following glucose stimulation. Surprisingly, although expression of a dominant-interfering dynamin mutant (Dyn/K44A) inhibited transferrin receptor endocytosis, it had no effect on phogringreen fluorescent protein localization in the basal or secretagogue-stimulated state. By contrast, co-expression of Dyn/ K44A with human growth hormone as an insulin secretory marker resulted in a marked inhibition of human growth hormone release by glucose, KCl, and a combination of multiple secretagogues. Moreover, serial pulse depolarization stimulated an increase in cell surface capacitance that was also blocked in cells expressing Dyn/K44A. Similarly, small interference RNA-mediated knockdown of dynamin resulted in marked inhibition of glucose-stimulated insulin secretion. Together, these data suggest the presence of a selective kiss and run mechanism of insulin release. Moreover, these data indicate a coupling between endocytosis and exocytosis in the regulation of ␤-cell insulin secretion.

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Section: Integral Membrane Proteins In Insulin Granules Do Notmentioning

confidence: 60%

Dynamin Is Functionally Coupled to Insulin Granule Exocytosis

Min

Leung

Tomás³

et al. 2007

Journal of Biological Chemistry

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“…In other systems, kinesin and kinesin-related proteins have been shown to interact directly or indirectly with signaltransducing proteins, including protein kinases. In some cases, the interaction influences the activity of the motor protein and, in others, the motor protein is crucial for the delivery of signaling molecules to their sites of action (Bowman et al, 2000;Day et al, 2000;Donelan et al, 2002;Morfini et al, 2002;Nagata et al, 1998;Setou et al, 2002;. The relationships documented here between kinesin II and CALK represent a useful system to learn more about the mechanisms that regulate the spatial and temporal localization of proteins in cilia and flagella during signal transduction.…”

Section: Discussionmentioning

confidence: 99%

Kinesin II and regulated intraflagellar transport ofChlamydomonasaurora protein kinase

Pan

Snell

2003

Journal of Cell Science

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The assembly and functioning of cilia and flagella depend on a complex system of traffic between the organelles and the cell body. Two types of transport into these organelles have been identified. The best characterized is constitutive: in a process termed intraflagellar transport (IFT), flagellar structural components are continuously carried into cilia and flagella on transport complexes termed IFT particles via the microtubule motor protein kinesin II. Previous studies have shown that the flagella of the unicellular green alga Chlamydomonas exhibit a second type of protein import that is regulated. During fertilization, the Chlamydomonas aurora protein kinase CALK undergoes regulated translocation from the cell body into the flagella. The motor that powers this second, regulated type of movement is unknown. Here, we have examined the cellular properties of the CALK in Chlamydomonas and used a kinesin II mutant to test the idea that the motor protein is essential for regulated translocation of proteins into flagella. We found that the CALK that is transported into flagella of wild-type gametes becomes part of a membrane-associated complex, that kinesin II is essential for the normal localization of this Chlamydomonasaurora protein kinase in unactivated gametes and that the cAMP-induced translocation of the protein kinase into flagella is disrupted in the fla10 mutants. Our results indicate that, in addition to its role in the constitutive transport of IFT particles and their cargo, kinesin II is essential for regulated translocation of proteins into flagella.

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“…Isolated rat islets or INS-1 [832/13] cells were infected with adenovirus and analyzed for insulin secretory activity by radioimmunoassay in both static and perifusion incubation experiments as described previously at either basal (2·8 mM) or stimulatory (16·7 mM) glucose ( 10 nM GLP-1 or 5µM glyburide as indicated) (Donelan et al 2002).…”

Section: In Vitro Insulin Secretion and Islet Perifusionmentioning

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

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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.

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Ca2+-dependent Dephosphorylation of Kinesin Heavy Chain on β-Granules in Pancreatic β-Cells

Cited by 92 publications

References 60 publications

Dynamin Is Functionally Coupled to Insulin Granule Exocytosis

Dynamin Is Functionally Coupled to Insulin Granule Exocytosis

Kinesin II and regulated intraflagellar transport ofChlamydomonasaurora protein kinase

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

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