Protein phosphorylation and the regulation of synaptic membrane traffic

Turner, Kathryn M.; Burgoyne, Robert D.; Morgan, Alan

doi:10.1016/s0166-2236(99)01436-8

Cited by 224 publications

(186 citation statements)

References 73 publications

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“…In particular, kinases involved in growth control are likely to modulate SNARE functions, presumably by the posttranslational modification of residues that participate in SNARE partnering or the binding of SNARE regulatory proteins (reviewed in Gerst, 1999;Turner et al, 1999;Klenchin and Martin, 2000). Numerous studies have outlined the possible involvement of kinases in the regulation of SNARE protein interactions (Hirling and Scheller, 1996;Shimazaki et al, 1996;Foster et al, 1998;Shuang et al, 1998;Risinger and Bennett, 1999;Chung et al, 2000) as well as the availability of SNAREs to participate in membrane trafficking events (Cabaniols et al, 1999;Foletti et al, 2000;Kataoka et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

t-SNARE Phosphorylation Regulates Endocytosis in Yeast

Gurunathan

Marash

Weinberger

et al. 2002

MBoC

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Earlier we demonstrated that activation of a ceramide-activated protein phosphatase (CAPP) conferred normal growth and secretion to yeast lacking their complement of exocytic v-SNAREs (Snc1,2) or bearing a temperature-sensitive mutation in an exocytic t-SNARE (Sso2). CAPP activation led to Sso dephosphorylation and enhanced the assembly of t-SNAREs into functional complexes. Thus, exocytosis in yeast is modulated by t-SNARE phosphorylation. Here, we show that endocytic defects in cells lacking the v-and t-SNAREs involved in endocytosis are also rescued by CAPP activation. Yeast lacking the Tlg1 or Tlg2 t-SNAREs, the Snc v-SNAREs, or both, undergo endocytosis after phosphatase activation. CAPP activation correlated with restored uptake of FM4-64 to the vacuole, the uptake and degradation of the Ste2 receptor after mating factor treatment, and the dephosphorylation and assembly of Tlg1,2 into SNARE complexes. Activation of the phosphatase by treatment with C 2 -ceramide, VBM/ELO gene inactivation, or by the overexpression of SIT4 was sufficient to confer rescue. Finally, we found that mutation of single PKA sites in Tlg1 (Ser31 to Ala31) or Tlg2 (Ser90 to Ala90) was sufficient to restore endocytosis, but not exocytosis, to snc cells. These results suggest that endocytosis is also modulated by t-SNARE phosphorylation in vivo.

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Section: Introductionmentioning

confidence: 99%

t-SNARE Phosphorylation Regulates Endocytosis in Yeast

Gurunathan

Marash

Weinberger

et al. 2002

MBoC

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“…Protein kinase C and protein kinase A sites on SNAP-25 affect refilling rates and size, respectively, of the primed pool of vesicles in chromaffin cells (15,16). Several SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)-binding proteins such as munc18, RIM1, and rabphilin undergo regulated phosphorylation, but it is not known whether phosphorylation affects function (10,11,17).Because the function of CAPS at a priming step in vesicle exocytosis may be regulated, we determined whether CAPS is phosphorylated. We show that CAPS is a phosphoprotein with functionally essential N-terminal phosphorylated Ser residues.…”

mentioning

confidence: 99%

“…Many proteins that function in evoked vesicle exocytosis are phosphoproteins (10,11). The neuronal SNARE proteins syntaxin 1A, VAMP-2, and SNAP-25 are phosphorylated by several protein kinases in vitro (12)(13)(14).…”

mentioning

confidence: 99%

CAPS Activity in Priming Vesicle Exocytosis Requires CK2 Phosphorylation

Nojiri

Loyet²,

Klenchin

et al. 2009

Journal of Biological Chemistry

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CAPS (Ca 2؉ -dependent activator protein for secretion) functions in priming Ca 2؉ -dependent vesicle exocytosis, but the regulation of CAPS activity has not been characterized. Here we show that phosphorylation by protein kinase CK2 is required for CAPS activity. Dephosphorylation eliminated CAPS activity in reconstituting Ca 2؉ -dependent vesicle exocytosis in permeable and intact PC12 cells. Ser-5, -6, and -7 and Ser-1281 were identified by mass spectrometry as the major phosphorylation sites in the 1289 residue protein. Ser-5, -6, and -7 but not Ser-1281 to Ala substitutions abolished CAPS activity. Protein kinase CK2 phosphorylated CAPS in vitro at these sites and restored the activity of dephosphorylated CAPS. CK2 is the likely in vivo CAPS protein kinase based on inhibition of phosphorylation by tetrabromo-2-benzotriazole in PC12 cells and by the identity of in vivo and in vitro phosphorylation sites. CAPS phosphorylation by CK2 was constitutive, but the elevation of Ca 2؉ in synaptosomes increased CAPS Ser-5 and -6 dephosphorylation, which terminates CAPS activity. These results identify a functionally important N-terminal phosphorylation site that regulates CAPS activity in priming vesicle exocytosis.Regulated neurotransmitter secretion is central to intercellular communication in the nervous system. Two types of secretory vesicles mediate neurotransmitter release; that is, synaptic vesicles that release transmitters such as glutamate at synapses and dense-core vesicles that release modulatory transmitters and neuropeptides at non-synaptic sites. Both types of secretory vesicles are recruited to docking sites on the plasma membrane where they are primed to a ready release state to undergo fusion in response to Ca 2ϩ elevations. Many of the proteins that mediate the targeting, docking, priming, and Ca 2ϩ -dependent fusion of vesicles with the plasma membrane function in both synaptic vesicle and dense-core vesicle pathways (1). CAPS-1 2 (also known as Cadps1) is a 1289-residue protein that reconstitutes Ca 2ϩ -triggered dense-core vesicle exocytosis in permeable neuroendocrine cells at a priming step (2-4). CAPS is required for secretion of a subset of transmitters in Caenorhabditis elegans (5) and Drosophila melanogaster (6) and for priming dense-core vesicle exocytosis in neuroendocrine cells (7) and synaptic vesicle exocytosis in neurons (8). Vesicle priming reactions are extensively modulated during physiological demand (9), but mechanisms that regulate CAPS function remain to be identified.Reversible protein phosphorylation is a major mechanism for the regulation of cellular processes including vesicle exocytosis. Many proteins that function in evoked vesicle exocytosis are phosphoproteins (10, 11). The neuronal SNARE proteins syntaxin 1A, VAMP-2, and SNAP-25 are phosphorylated by several protein kinases in vitro (12)(13)(14). Protein kinase C and protein kinase A sites on SNAP-25 affect refilling rates and size, respectively, of the primed pool of vesicles in chromaffin cells (15,16). Several SNARE...

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“…The control of synaptic vesicle cycle by increasing the number of vesicles in RRP through mobilization of vesicles from the RP (regulation of the releasable pools), or by increasing the number of docked vesicles that are ready for fusion (release probability of docked vesicles) is one way to regulate neurotransmitter release (Turner et al, 1999). The filling of the RRP, measured as recovery from depletion, is enhanced by elevated [Ca 2+ ]j (Von Ruden and Neher, 1993).…”

Section: Mechanism Of Granules Mobilizationmentioning

confidence: 99%

“…Synapsin I and H are phosphorylated by both PKA and CaMK n (Nicol et al, 1997;. Although PKA can phosphorylate synapsin I and II, the phosphorylation of synapsin I by CaMK II that is considerd to be the main way to mediate the release of synaptic vesicles (Turner et al, 1999). Therefore, the association of synapsin I with SVs has been characterized in detail.…”

Section: Granules Mobilization Due To Synapsins Activationmentioning

confidence: 99%

Arginine vasopressin-induced glucagon release: interaction with glucose and cyclic AMP-dependent protein kinase

Abu-Basha

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Protein phosphorylation and the regulation of synaptic membrane traffic

Cited by 224 publications

References 73 publications

t-SNARE Phosphorylation Regulates Endocytosis in Yeast

t-SNARE Phosphorylation Regulates Endocytosis in Yeast

CAPS Activity in Priming Vesicle Exocytosis Requires CK2 Phosphorylation

Arginine vasopressin-induced glucagon release: interaction with glucose and cyclic AMP-dependent protein kinase

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