Syntaxin 1A and 1B display distinct distribution patterns in the rat peripheral nervous system

Aguado, Fernando; Majó, Glòria; Ruiz-Montasell, Bonaventura; Llorens, Jordi; Marsal, Jordi; Blasi, Juan

doi:10.1016/s0306-4522(98)00247-4

Cited by 53 publications

(51 citation statements)

References 49 publications

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“…We also found SNAP-25 to be modified by methionine excision and acetylation, which is in agreement with a previous study (24). Syntaxin-1 also exists in two isoforms (1A and 1B) (14,29). Peptides specific for both forms were identified via MS/MS in all samples.…”

Section: Resultssupporting

confidence: 92%

“…The protein target can be altered or expanded by changing antibodies, adding stable-isotope-labeled standards of modified protein forms or protein complex interaction partners, or changing the fractionation method to study different subtypes of cells or specific cell compartments (13). This is of particular interest when studying the SNARE complex proteins, as it has been shown that different combinations of SNARE protein isoforms interact with dissimilar affinities and are differentially distributed in defined areas of the central nervous system, suggesting specialized functions of these isoforms (29). Other SNARE protein isoforms such as SNAP-25A and -25B have very different expression during embryonic and early postnatal development: SNAP-25A is the predominant species during embryonic and early postnatal development, whereas SNAP-25B transcripts increase dramatically after the first postnatal week to become the majority of SNAP-25 mRNA in adult brain (38,39).…”

Section: Discussionmentioning

confidence: 99%

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P1‐155: Targeting Synaptic Pathology With a Novel Affinity Mass Spectrometry Approach

Brinkmalm

Honer

et al. 2014

Alzheimer's & Dementia

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We report a novel strategy for studying synaptic pathology by concurrently measuring levels of four SNARE complex proteins from individual brain tissue samples. This method combines affinity purification and mass spectrometry and can be applied directly for studies of SNARE complex proteins in multiple species or modified to target other key elements in neuronal function. We use the technique to demonstrate altered levels of presynaptic proteins in Alzheimer disease patients and prion-infected mice. Molecular & Cellular Proteomics 13: 10.1074/mcp. M114.040113, 2584-2592, 2014.One prominent pathological feature of neuropsychiatric disorders such as Alzheimer disease (AD) 1 is severe synaptic loss (1-3). Previous reports of AD patients have shown that presynaptic dysfunction might occur early in the disease process (1, 4). Cortical synapse pathology has also been shown to correlate to the severity of dementia more closely than other pathological hallmarks of AD such as plaques and neurofibrillary tangles (5, 6). The SNARE proteins are essential components for the regulation of neurotransmitter exocytosis at the presynaptic site (7). Animal models suggest that changed expression or modification of SNARE complex proteins (synaptosomal-associated protein 25 (SNAP-25), syntaxin-1, and vesicle-associated membrane protein (VAMP)) alters synaptic function and is an interesting target for the development of therapeutics for neuropsychiatric illness (8, 9). The constituents of the SNARE complex are either localized in synaptic vesicles (VAMPs) or anchored at the presynaptic plasma membrane (SNAP-25 and syntaxin). The SNARE proteins are tightly assembled, and subsequent neurotransmitter release of the complex is quickly dissociated by N-ethylmaleimide-sensitive factor (7, 10 -12). Because they are both strongly associated into complexes and membrane associated, the SNARE proteins are difficult to analyze via mass spectrometry, which is incompatible with most detergents necessary for the solubilization of proteins. Each SNARE complex protein exists in several isoforms that are differently distributed within the central nervous system (13-18). Posttranslational modifications and truncated variants of the SNARE proteins make investigation of the protein expression even more complicated.In this study we developed an approach for the characterization and concurrent quantification of SNARE complex proteins that combines affinity purification by immunoprecipitation and mass spectrometry (IP-MS). We used precipitation with monoclonal antibodies against SNAP-25 to target the SNARE complex proteins and nanoflow LC-tandem mass spectrometry (LC-MS/MS) to characterize the co-immunoprecipitated interaction partners. Selected reaction monitoring (SRM) on a triple quadrupole mass spectrometer coupled to a microflow LC system was used for quantification of the SNARE proteins. To demonstrate the usability of the IP-MS method, we performed a comparison of SNARE complex protein levels in brain tissue from AD patients and agematched controls, a...

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Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

P1‐155: Targeting Synaptic Pathology With a Novel Affinity Mass Spectrometry Approach

Brinkmalm

Honer

et al. 2014

Alzheimer's & Dementia

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“…Syntaxin 1B is the most reasonable candidate for such a substitution. The two syntaxin isoforms, HPC-1/syntaxin 1A and syntaxin 1B, are expressed in a combinatorial manner in the central and peripheral nervous system, with some regions of overlap (RuizMontasell et al, 1996;Aguado et al, 1999). Genetic defects in HPC-1/syntaxin 1A did not change the syntaxin 1B content or the expression of other exocytosis-related proteins (Fujiwara et al, 2006), indicating a reduction in the total amount of syntaxin 1 and the downregulation of exocytotic function.…”

Section: Discussionmentioning

confidence: 99%

Impairment of Catecholamine Systems during Induction of Long-Term Potentiation at Hippocampal CA1 Synapses in HPC-1/Syntaxin 1A Knock-out Mice

Mishima

Fujiwara²,

Kofuji³

et al. 2012

J. Neurosci.

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The membrane protein HPC-1/syntaxin 1A is believed to play a key role in synaptic vesicle exocytosis, and it was recently suggested to be required for synaptic plasticity. Despite evidence for the function of HPC-1/syntaxin 1A in synaptic plasticity, the underlying cellular mechanism is unclear. We found that although fast synaptic transmission and long-term depression were unaffected, HPC-1/syntaxin 1A knock-out (STX1A Ϫ/Ϫ ) mice showed impaired long-term potentiation (LTP) in response to theta-burst stimulation in CA1 hippocampal slices. The impairment in LTP was rescued by the application of forskolin, an adenylyl cyclase activator, or more robust stimulation, suggesting that cAMP/protein kinase A signaling was suppressed in these mice. In addition, catecholamine release from the hippocampus was significantly reduced in STX1A Ϫ/Ϫ mice. Because HPC-1/syntaxin 1A regulates exocytosis of dense-core synaptic vesicles, which contain neuromodulatory transmitters such as noradrenaline, dopamine and 5-HT, we examined the effect of neuromodulatory transmitters on LTP induction. Noradrenaline and dopamine enhanced LTP induction in STX1A Ϫ/Ϫ mice, whereas catecholamine depletion reduced LTP induction in wild-type mice. Theses results suggest that HPC-1/syntaxin 1A regulates catecholaminergic systems via exocytosis of dense-core synaptic vesicles, and that deletion of HPC-1/syntaxin 1A causes impairment of LTP induction.

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“…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%

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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Syntaxin 1A and 1B display distinct distribution patterns in the rat peripheral nervous system

Cited by 53 publications

References 49 publications

P1‐155: Targeting Synaptic Pathology With a Novel Affinity Mass Spectrometry Approach

P1‐155: Targeting Synaptic Pathology With a Novel Affinity Mass Spectrometry Approach

Impairment of Catecholamine Systems during Induction of Long-Term Potentiation at Hippocampal CA1 Synapses in HPC-1/Syntaxin 1A Knock-out Mice

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

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