Regulation of Exocytosis by Cyclin-dependent Kinase 5 via Phosphorylation of Munc18*

@article{Fletcher1999RegulationOE,
  title={Regulation of Exocytosis by Cyclin-dependent Kinase 5 via Phosphorylation of Munc18*},
  author={Allan Fletcher and Rong Shuang and David R Giovannucci and Lin-hua Zhang and Mary A. Bittner and Edward L. Stuenkel},
  journal={The Journal of Biological Chemistry},
  year={1999},
  volume={274},
  pages={4027 - 4035}
}
Munc18a, a mammalian neuronal homologue ofSaccharomyces cerevisiae Sec1p protein, is essential for secretion, likely as a result of its high affinity interaction with the target SNARE protein syntaxin 1a (where SNARE is derived from SNAP receptor (the soluble N-ethylmaleimide-sensitive fusion protein)). However, this interaction inhibits vesicle SNARE interactions with syntaxin that are required for secretory vesicles to achieve competency for membrane fusion. As such, regulation of the… 
Cyclin-Dependent Kinase 5 Phosphorylation of Human Septin SEPT5 (hCDCrel-1) Modulates Exocytosis
TLDR
It is reported that p35 associates with SEPT5 in GST (glutathione S-transferase)-pull-down and coimmunoprecipitation assays and suggests that Cdk5 phosphorylation of human sept5 at S327 plays a role in modulating exocytotic secretion.
Co-purification and localization of Munc18-1 (p67) and Cdk5 with neuronal cytoskeletal proteins
Munc18-1 (p67, nSec1, rbSec1), a neuron-specific 67kDa protein was independently identified as a syntaxin-binding protein, and as a component that co-purifies with, and regulates the kinase activity
The Stimulus-induced Tyrosine Phosphorylation of Munc18c Facilitates Vesicle Exocytosis*
TLDR
Data support a novel and conserved mechanism for the dissociation of Munc18c-Syntaxin 4 complexes in a stimulus-dependent manner to facilitate the increase in Syntaxin 4-VAMP2 association and to promote vesicle/granule fusion.
A mechanism of Munc18b–syntaxin 3–SANP25 complex assembly in regulated epithelial secretion
TLDR
A novel regulatory mechanism in which phosphorylation of Munc18b operates vesicle docking and fusion in regulated exocytosis is suggested, leading to an assembly of functional Munc 18b–syntaxin 3–SNAP25–VAMP2 membrane fusion machinery.
Regulation of syntaxin 1 A – munc 18 complex for SNARE pairing in HEK 293 cells
The formation and dissolution of SNARE protein complexes is essential for Ca2+-triggered fusion of neurotransmitter-filled vesicles at the presynaptic membrane. Among the pre-synaptic SNARE proteins,
Dynamic Conformational Changes in MUNC18 Prevent Syntaxin Binding
TLDR
The proposed conformation is a syntaxin-non-binding conformation of munc18a that is induced by the phosphomimetic mutations, which makes syntaxin binding energetically and sterically unfavorable.
Regulation of SNARE assembly by protein phosphorylation
Protein phosphorylation is emerging as an important regulatory mechanism that controls the secretory pathway. It enables coupling between the vesicular transport machinery and signaling cascades that
Ca2+-dependent Phosphorylation of Syntaxin-1A by the Death-associated Protein (DAP) Kinase Regulates Its Interaction with Munc18*
TLDR
The results suggest that syntaxin is a DAP kinase substrate and provide a novel signal transduction pathway by which syntaxin function could be regulated in response to intracellular [Ca2+] and synaptic activity.
Analysis of the Munc18b-Syntaxin Binding Interface
TLDR
Over-expression of Munc18b S48D inhibited transport of influenza hemagglutinin to the apical surface of Madin-Darby canine kidney II cells, which express syntaxin 2 abundantly, but not of Caco-2 cells, in which syntaxin 3 is the major apical target SNARE (soluble NSF (N-ethylmaleimide sensitive factor) attachment protein receptors).
Munc18a: Munc-y business in mediating exocytosis.
The precise sequence of molecular events underlying release of neurotransmitter in neurons is yet to be fully understood. This process, called exocytosis, is tightly controlled by a number of
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 49 REFERENCES
Regulation of Munc-18/Syntaxin 1A Interaction by Cyclin-dependent Kinase 5 in Nerve Endings*
The Munc-18-syntaxin 1A complex has been postulated to act as a negative control on the regulated exocytotic process because its formation blocks the interaction of syntaxin with vesicle SNARE
Phosphorylation of Munc-18/n-Sec1/rbSec1 by Protein Kinase C
TLDR
It is shown that recombinant Munc-18 is phosphorylated by conventional PKC in a Ca- and phospholipid-dependent manner in a cell-free system and this results suggest that the PKC-catalyzed phosphorylation of Munm-18 plays an important role in regulating the interaction of MunC-18 with syntaxin and thereby the docking and/or the fusion of synaptic vesicles with the presynaptic plasma membrane.
Mints, Munc18-interacting Proteins in Synaptic Vesicle Exocytosis*
TLDR
The data suggest a model whereby local production of phosphatidylinositol phosphates may trigger the binding of vesicles to the active zone via the Mint·Munc18-1 complex in conjunction with syntaxin 1.
Synaptic vesicle fusion complex contains unc-18 homologue bound to syntaxin
TLDR
The discovery of a brain protein of relative molecular mass 67,000 (67K) which binds stably to syntaxin suggests that Munc-18 is a previously unidentified essential component of the synaptic vesicle fusion protein complex.
n-Sec1: a neural-specific syntaxin-binding protein.
TLDR
Findings indicate that n-Sec1 is a neural-specific, syntaxin-binding protein that may participate in the regulation of synaptic vesicle docking and fusion.
A Novel Ubiquitous Form of Munc-18 Interacts with Multiple Syntaxins.
TLDR
The lack of specificity of the interactions between syntaxins and Munc-18s indicates that specificity of membrane trafficking reactions is not dependent on this interaction, and it is demonstrated that neural and non-neural tissues have distinct forms of MunC-18, which may function in different types of exocytosis.
A rat brain Sec1 homologue related to Rop and UNC18 interacts with syntaxin.
TLDR
The function of proteins of the Sec1 family in membrane fusion involves an interaction with a T-SNARE, thought to form the core of the docking-fusion complex in synaptic vesicle exocytosis.
rbSec1A and B colocalize with syntaxin 1 and SNAP-25 throughout the axon, but are not in a stable complex with syntaxin
TLDR
The results suggest that the function of rbSec1, syntaxin 1, and SNAP-25 is not restricted to synaptic vesicle exocytosis at the synapse, and that rbsec1 and syntaxin 2 are not stably associated.
Distinct domains of syntaxin are required for synaptic vesicle fusion complex formation and dissociation
TLDR
It is demonstrated that unique, yet overlapping, domains of syntaxin are required to form these complexes, consistent with the hypothesis that conformational changes in syntaxin, resulting from protein-protein interactions and ATP hydrolysis by NSF, mediate neurotransmitter release.
Rop, a drosophila homolog of yeast Sec1 and vertebrate n-Sect/Munc-18 proteins, is a negative regulator of neurotransmitter release in vivo
TLDR
It is proposed that the Drosophila n-Sec1/Munc-18 homolog plays a negative role in neurotransmitter release in vivo, in addition to its previously identified positive function, possibly by modulation of docking of synaptic vesicles or activation of a pre-fusion complex at the active zone.
...
1
2
3
4
5
...