Differential Distribution of Syntaxin Isoforms 1A and 1B in the Rat Central Nervous System

Ruiz-Montasell, Bonaventura; Aguado, Fernando; Majó, Glòria; Chapman, Edwin R.; Canals, Josep M.; Marsal, Jordi; Blasi, Juan

doi:10.1111/j.1460-9568.1996.tb01548.x

Cited by 67 publications

(55 citation statements)

References 36 publications

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“…The fractions were probed by Western blot with ␣HPC-1 and ␣Psyn. As shown previously (Ruiz-Montasell et al, 1996), ␣HPC-1 recognized a doublet of proteins of 35-38 kDa with the lower band being syntaxin 1A (syn1A) and the upper band corresponding to syntaxin 1B (syn1B) (Fig. 2 A, lane 1).…”

Section: Previous Reportssupporting

confidence: 82%

“…Syn1A and syn1B are closely related isoforms with a high level of sequence homology (84% identity) (Bennett et al, 1993a). The two syntaxin isoforms are expressed in a combinatorial manner in the CNS and PNS, with regions of overlapping and regions of distinct distribution (Ruiz-Montasell et al, 1996;Aguado et al, 1999). The physiological significance of the occurrence of these two close isoforms and their differential distribution remains to be elucidated.…”

Section: Previous Reportsmentioning

confidence: 99%

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Phosphorylated Syntaxin 1 Is Localized to Discrete Domains Along a Subset of Axons

et al. 2000

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Syntaxin 1 is a SNARE protein that plays a central role in synaptic vesicle (SV) exocytosis. We generated an antibody that specifically recognizes a casein kinase II-mediated phosphorylation on serine-14 of syntaxin 1. In this report we show that this phosphorylation occurs in vivo and is developmentally regulated in the rat brain, rising to a level of 40% of the total syntaxin in adult animals. Phosphorylated syntaxin is preferentially associated with SNAP-25 and localizes to discrete domains of the axonal plasma membrane that do not colocalize with pools of synaptic vesicles. These phosphosyntaxin domains may define fusion sites for a novel class of vesicles outside classical active zones.

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Section: Previous Reportssupporting

confidence: 82%

Section: Previous Reportsmentioning

confidence: 99%

Phosphorylated Syntaxin 1 Is Localized to Discrete Domains Along a Subset of Axons

et al. 2000

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“…DCC antibodies immunoprecipitated in brain lysates a band of 35 kDa, which corresponded to Sytx1A and 1B isoforms (WB with the HPC-1 Mab; Fig. 1 A) (Ruiz-Montasell et al, 1996). A 180 kDa band corresponding to DCC was identified after immunoprecipitation with anti-Sytx1 antibodies (Fig.…”

Section: Resultsmentioning

confidence: 92%

A Signaling Mechanism Coupling Netrin-1/Deleted in Colorectal Cancer Chemoattraction to SNARE-Mediated Exocytosis in Axonal Growth Cones

et al. 2011

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Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-offunction experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

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“…Possible Implications for Synaptic Function-Although syntaxin 1A and 1B share 93% similarity, mediate an identical role in exocytosis, and display an identical ability to shift the steady state inactivation potential of the N-type channel, they differ in both their distribution patterns throughout the central and peripheral nervous systems (46,47), and in their regulation following the induction of long term potentiation (48). Moreover, syntaxin 1A and 1B differentially affect G-protein inhibition of N-type calcium channels in transient expression systems and in chick DRG neurons (27).…”

Section: Discussionmentioning

confidence: 99%

Molecular Determinants of Syntaxin 1 Modulation of N-type Calcium Channels

Jarvis

Barr

Feng³

et al. 2002

Journal of Biological Chemistry

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We have previously reported that syntaxin 1A, a component of the presynaptic SNARE complex, directly modulates N-type calcium channel gating in addition to promoting tonic G-protein inhibition of the channels, whereas syntaxin 1B affects channel gating but does not support G-protein modulation (Jarvis, S. E., and Zamponi, G. W. (2001) J. Neurosci. 21, 2939 -2948). Here, we have investigated the molecular determinants that govern the action of syntaxin 1 isoforms on N-type calcium channel function. In vitro evidence shows that both syntaxin 1 isoforms physically interact with the G-protein ␤ subunit and the synaptic protein interaction (synprint) site contained within the N-type calcium channel domain II-III linker region. Moreover, in vitro evidence suggests that distinct domains of syntaxin participate in each interaction, with the COOH-terminal SNARE domain (residues 183-230) binding to G␤ and the N-terminal (residues 1-69) binding to the synprint motif of the channel. Electrophysiological analysis of chimeric syntaxin 1A/1B constructs reveals that the variable NH 2 -terminal domains of syntaxin 1 are responsible for the differential effects of syntaxin 1A and 1B on N-type calcium channel function. Because syntaxin 1 exists in both "open" and "closed" conformations during exocytosis, we produced a constitutively open form of syntaxin 1A and found that it still promoted G-protein inhibition of the channels, but it did not affect N-type channel availability. This state dependence of the ability of syntaxin 1 to mediate N-type calcium channel availability suggests that syntaxin 1 dynamically regulates N-type channel function during various steps of exocytosis. Finally, syntaxin 1A appeared to compete with G␥ for the G␤ subunit both in vitro and under physiological conditions, suggesting that syntaxin 1A may contain a G-protein ␥ subunit-like domain.Calcium influx through N-type calcium channels is a key step in neurotransmitter release from presynaptic nerve termini (1, 2). In mammalian neurons, these channels physically associate with proteins of the presynaptic vesicle docking and release machinery, notably syntaxin 1, soluble NSF attachment protein (SNAP) 1 25, synaptotagmin, cysteine string protein, Rab3-interacting molecules (RIMs), and RIM-binding protein 2, thus localizing synaptic vesicles close to the source of extracellular calcium (3-12). The interaction of SNAP25 and syntaxin 1A or 1B with the N-type calcium channel acts as a negative feedback mechanism, such that N-type calcium channel availability is reduced in the presence of these proteins, which is reflected as a negative shift in the half-inactivation potential of the channels (13-16). We have recently shown that this effect is abolished when both syntaxin 1 and SNAP25 are present concomitantly, or following coexpression of nSec-1 (also called , and that protein kinase C-dependent phosphorylation of the channel abolishes the shift in steady state inactivation (16). Together, these findings indicate that the effects of syntaxin 1 on channel avail...

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Differential Distribution of Syntaxin Isoforms 1A and 1B in the Rat Central Nervous System

Cited by 67 publications

References 36 publications

Phosphorylated Syntaxin 1 Is Localized to Discrete Domains Along a Subset of Axons

Phosphorylated Syntaxin 1 Is Localized to Discrete Domains Along a Subset of Axons

A Signaling Mechanism Coupling Netrin-1/Deleted in Colorectal Cancer Chemoattraction to SNARE-Mediated Exocytosis in Axonal Growth Cones

Molecular Determinants of Syntaxin 1 Modulation of N-type Calcium Channels

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