Disruption of syntaxin-mediated protein interactions blocks neurotransmitter secretion

O’Connor, Vincent; Heuss, Christian; Bello, W. M. De; Dresbach, Thomas; Charlton, Milton P.; Hunt, J. H.; Pellegrini, Lorenzo; Hodel, Alois; Burger, Max M.; Betz, Heinrich; Augustine, G. J.; Schäfer, Theo

doi:10.1073/pnas.94.22.12186

Cited by 96 publications

(89 citation statements)

References 42 publications

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“…However, the three sites necessary for binding and cleavage by Bot N/C (Schiavo et al, 1995;O'Connor et al, 1997), which are present on Nt-Syr1 (Leyman et al, 1999) and associated with sensitivity to the toxin, are poorly conserved in OSM1/SYP61 ( Figure 12B). Although it remains unproven that OSM1/SYP61 is not sensitive to Bot N/C, this finding suggests that there may be another Arabidopsis SNARE protein that has a similar function, because Leyman et al (1999) were able to inhibit ABA-induced Cl Ϫ channel current in tobacco guard cells with Bot N/C treatment.…”

Section: Discussionmentioning

confidence: 99%

“…It is interesting as well that syntaxin appears to be required for tethering to membrane sites of the Ca 2ϩ channel that affects neurotransmitter release, ensuring G-protein OSM1/SYP61, Arabidopsis; STX6_MOUSE, syntaxin 6 from mouse; STX6_HUMAN, syntaxin 6 from human; STX10_HUMAN, syntaxin 10 from human. Sequences shown above the aligned sequences are two predicted Clostridium botulinum toxin C1 recognition sites (FMEEFFEQVE and ELEDMLESGN, respectively) and a cleavage site (AVKYQSKAR) from squid syntaxin (Schiavo et al, 1995;O'Connor et al, 1997). (C) Sequence alignment in the t-SNARE coiled-coil domain.…”

Section: Discussionmentioning

confidence: 99%

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OSM1/SYP61: A Syntaxin Protein in Arabidopsis Controls Abscisic Acid–Mediated and Non-Abscisic Acid–Mediated Responses to Abiotic Stress

et al. 2002

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To identify the genetic loci that control salt tolerance in higher plants, a large-scale screen was conducted with a bialaphos marker-based T-DNA insertional collection of Arabidopsis ecotype C24 mutants. One line, osm1 (for osmotic stress-sensitive mutant), exhibited increased sensitivity to both ionic (NaCl) and nonionic (mannitol) osmotic stress in a root-bending assay. The osm1 mutant displayed a more branched root pattern with or without stress and was hypersensitive to inhibition by Na ؉ , K ؉ , and Li ؉ but not Cs ؉ . Plants of the osm1 mutant also were more prone to wilting when grown with limited soil moisture compared with wild-type plants. The stomata of osm1 plants were insensitive to both ABA-induced closing and inhibition of opening compared with wild-type plants. The T-DNA insertion appeared in the first exon of an open reading frame on chromosome 1 ( F3M18.7 , which is the same as AtSYP61 ). This insertion mutation cosegregated closely with the osm1 phenotype and was the only functional T-DNA in the mutant genome. Expression of the OSM1 gene was disrupted in mutant plants, and abnormal transcripts accumulated. Gene complementation with the native gene from the wild-type genome completely restored the mutant phenotype to the wild type. Analysis of the deduced amino acid sequence of the affected gene revealed that OSM1 is related most closely to mammalian syntaxins 6 and 10, which are members of the SNARE superfamily of proteins required for vesicular/target membrane fusions. Expression of the OSM1 promoter:: ␤ -glucuronidase gene in transformants indicated that OSM1 is expressed in all tissues except hypocotyls and young leaves and is hyperexpressed in epidermal guard cells. Together, our results demonstrate important roles of OSM1/SYP61 in osmotic stress tolerance and in the ABA regulation of stomatal responses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

OSM1/SYP61: A Syntaxin Protein in Arabidopsis Controls Abscisic Acid–Mediated and Non-Abscisic Acid–Mediated Responses to Abiotic Stress

et al. 2002

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“…These toxins act as proteases that cleave one of the SNARE proteins, either syntaxin, SNAP-25 or synaptobrevin. 3 These and other observations 4,5 indicate that the proteins of the 7S complex are necessary for neurotransmitter release. Is there similar experimental data to support a role for the additional proteins of the 20S complex, SNAP and NSF, in neurotransmitter release?…”

mentioning

confidence: 86%

SNARE proteins and the timing of neurotransmitter release

Schweizer¹,

Augustine

1998

Mol Psychiatry

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The SNARE complex proteins have been implicated in exocytotic neurotransmitter release and other forms of membrane fusion. Recent work shows that NSF, the ATPase of the SNARE complex, regulates the kinetics of neurotransmitter release and can thereby control the integrative properties of synapses.Time is one of the most critical parameters in the functioning of the brain. Information transfer on the timescale of milliseconds (10 −3 seconds) is typical throughout the brain and in certain brain regions, such as the auditory brainstem, time differences on the order of microseconds (10 −6 seconds) are used to define the frequency and location of perceived sounds. Thus information processing not only depends on a fast underlying process but also on the precise timing of synaptic activity. Such high temporal fidelity must rely upon very finely-regulated molecular mechanisms. However, until recently the identity of these mechanisms has been remarkably elusive. We summarize here our recent experiments that provide the first clues about the identity of the molecular timers of synaptic transmission.Synaptic transmission occurs when synaptic vesicles containing neurotransmitters fuse with the plasma membrane of a neuron, causing the neurotransmitters to be released onto downstream neurons and other target cells. Biochemical and molecular biological approaches have identified a group of presynaptic proteins that may be key players in neurotransmitter release. A soluble ATPase, called NSF (N-ethylmaleimide Sensitive Factor) binds, via another protein called SNAP (Soluble NSF Attachment Protein) to its membrane receptors, known as SNAREs (SNAP Receptors). Two of these SNAREs-syntaxin and SNAP-25 (for synaptosome-associated protein of 25-kDa molecular weight)-are found on the plasma membrane and another SNARE-synaptobrevin or VAMP (vesicleassociated membrane protein)-is in the membrane of the synaptic vesicles. In vitro experiments indicate that these proteins associate in various combinations 1 (Figure 1). The SNAREs can bind together to form the so-called 7S complex and addition of the soluble NSF and SNAP leads to the formation of a larger, 20S complex. This 20S complex breaks apart when NSF Correspondence: FE Schweizer, Dept Neurobiology, UCLA, Box 951763, Los Angeles, CA 90095-1763, USA. E-mail: felixsȰ-ucla.edu hydrolyzes ATP. Because SNAREs are found on both the synaptic vesicle membrane and the plasma membrane, it has been postulated that the various SNARE complexes mediate the interaction between the two membranes before fusion and thus may be necessary for neurotransmitter release. 2 Evidence for a role for SNARE proteins in neurotransmitter release has come from a variety of sources. The most compelling indication of the central importance of the three membrane SNARE proteins is that these proteins are remarkably specific targets of tetanus and botulinum toxins, a group of potent neurotoxins that completely paralyze neurotransmitter release. These toxins act as proteases that cleave one of the SNARE proteins, either...

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“…Binding of Clostridium neurotoxins and toxin cleavage of Syntaxin 1 or Synaptobrevin 1 blocks neurotransmitter release (Montecucco & Schiavo, 1995) but does not affect the number of vesicles docked at the nerve terminals. Cleavage of SNAP-25 by BotN\A affects only the late, Ca# + -dependent stages of exocytosis (Banerjee et al, 1996b ;O'Connor et al, 1997). Shiavo et al (1997) have suggested that, once docked, the Ca# + -dependent ' clamp ' effected by Synaptotagmin might bridge the primed SNARE complex.…”

Section: New Perspectives On Snare Functionmentioning

confidence: 99%

“…The larger part of each toxin comprises a permease that mediates transfer of the toxin protease across the plasma membrane. Each toxin then cleaves a unique protein target (Schiavo et al, 1992 ;Blasi et al, 1993 ;Binz et al, 1994 ;Yamasaki et al, 1994a-c) and this specificity has provided a remarkably powerful set of tools for probing SNARE function both in vitro (Hayashi et al, 1994) and in vivo (O'Connor et al, 1997 ;Stanley & Mirotznik, 1997).…”

Section: Snares and Associatesmentioning

confidence: 99%

Tansley Review No. 108

1999

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Eukaryotic cells share a set of secretory pathways for the flux of membrane and protein material. In 1993, ideas about the functioning of three major proteins of the neurosecretory complex were consolidated in the SNARE hypothesis, which proposed that the interaction of these proteins provides both the specificity for vesicle targeting and the molecular machinery for fusion between vesicle and target membranes. Subsequetly, the organization, molecular mechanics and control of vesicle trafficking have become topics of intense research, and the hypothesis has evolved to accommodate new discoveries from the analysis of secretion in yeast and mammals. It is likely to be challenged again as more information comes to light about secretory processes in plants. New tools for measuring and manipulating vesicle traffic and secretion are now being used, drawing on in vivo fluorescence and capacitance recording as well as genetic engineering. These new technologies have already begun to yield details wholly unexpected from past studies. Here we focus on recent findings relating to the mechanisms of vesicle trafficking and the background to these developments, highlighting both current understanding of the molecular events of secretion and the gaps therein, as well as discussing emerging themes from work with plants.

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Disruption of syntaxin-mediated protein interactions blocks neurotransmitter secretion

Cited by 96 publications

References 42 publications

OSM1/SYP61: A Syntaxin Protein in Arabidopsis Controls Abscisic Acid–Mediated and Non-Abscisic Acid–Mediated Responses to Abiotic Stress

OSM1/SYP61: A Syntaxin Protein in Arabidopsis Controls Abscisic Acid–Mediated and Non-Abscisic Acid–Mediated Responses to Abiotic Stress

SNARE proteins and the timing of neurotransmitter release

Tansley Review No. 108

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