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At least 217 records · Page 12Linked to original sources
PubMed2007

Acute sublethal global hypoxia induces transient increase of GAP-43 immunoreactivity in the striatum of neonatal rats.

We assessed immunoreactivity (IR) in the cerebral cortex (CC), hippocampus (Hipp), and striatum (ST) of a growth-associated protein, GAP-43, and of proteins of the synaptic vesicle fusion complex: VAMP-2, Syntaxin-1, and SNAP-25 (SNARE proteins) throughout postnatal development of rats after submitting the animals to acute global postnatal hypoxia (6.5% O(2), 70 min) at postnatal day 4 (PND4). In the CC only the IR of the SNARE protein SNAP-25 increased significantly with age. The hypoxic animals showed the same pattern of IR for SNAP-25, although with lower levels at PND11, and also a significant increase of VAMP-2. SNAP-25 (control): PND11 P < 0.001 vs. PND18, 25, and 40, SNAP-25 (hypoxic): P < 0.001 vs. PND18, 25, and 40; VAMP-2 (hypoxic): P < 0.05 PND11 vs. PND18, and P < 0.01 vs. PND25 and PND40; one-way ANOVA and Bonferroni post-test. In the Hipp, SNAP-25 and syntaxin-1 increased significantly with age, reaching a plateau at PND25 through PND40 in control animals (one-way ANOVA: syntaxin-1: P = 0.043; Bonferroni: NS; SNAP-25: P = 0.013; Bonferroni: P < 0.01 PND11 vs. PND40). Hypoxic rats showed higher levels of significance in the one-way ANOVA than controls (syntaxin-1: P = 0.009; Bonferroni: P < 0.05 PND11 vs. PND25 and P < 0.001 PND11 vs. PND40). In the ST, GAP-43 differed significantly among hypoxic and control animals and the two-way ANOVA revealed significant differences with age (F = 3.23; P = 0.037) and treatment (F = 4.84; P = 0.036). VAMP-2 expression also reached statistical significance when comparing control and treated animals (F = 6.25, P = 0.018) without changes regarding to age. Elevated plus maze test performed at PND40 indicated a lower level of anxiety in the hypoxic animals. At adulthood (12 weeks) learning, memory and locomotor abilities were identical in both groups of animals. With these results, we demonstrate that proteins of the presynaptic structures of the ST are sensitive to acute disruption of homeostatic conditions, such as a temporary decrease of the O(2) concentration. Modifications in the activity of these proteins could contribute to the long term altered responses to stress due to acute hypoxic insult in the neonatal period.

Acute Disease↗
PubMed1993

Molecular cloning of human epimorphin: identification of isoforms and their unique properties.

Epithelial-mesenchymal interactions are crucial for various epithelial tissue organizations and epimorphin is one of the important signaling molecules from the mesenchyme. The sequence analysis of a human homologue revealed that both of primary and predicted secondary structures of epimorphin are highly conserved among species and this molecule has some isoforms including a putative soluble type. I found that human epimorphins also have a large discrepancy in molecular masses as the case of mouse (around 33kD are predicted by the sequences whereas two protein bands of 60-70kD and 150kD are detected in the cells), and it can be explained, at least in part, by the SDS-resistant complexes formed in the microsomal membranes.

Amino Acid Sequence↗
PubMed1995

Involvement of HPC-1/syntaxin-1A antigen in transmitter release from PC12h cells.

We examined the effect of antiserum against HPC-1/Syntaxin-1A on the norepinephrine release from digitonin-permeabilized PC12h cells. PC12h cells were permeabilized with digitonin and preincubated with nonimmunized serum or antiserum against HPC-1. The release of norepinephrine was measured in the presence or absence of calcium. The calcium-dependent norepinephrine release was increased in the cells preincubated with anti HPC-1 antiserum. However, with a higher concentration of anti HPC-1 antiserum, the calcium-dependent norepinephrine release was decreased, possibly because of a nonspecific effect. In the case of purified IgG, the same results were obtained. These findings suggested that HPC-1 plays an important role in the exocytosis of transmitter presumably by suppressing the membrane fusion process between the synaptic vesicle and presynaptic membrane.

Analysis of Variance↗
PubMed1995

Expression of syntaxin 4 in rat skeletal muscle and rat skeletal muscle cells in culture.

Syntaxins are a family of membrane proteins believed to participate in docking/fusing of arriving vesicles during membrane sorting and secretion. Of the six mammalian syntaxins known, only brain syntaxin 1A/1B has been biochemically characterized in its endogenous form. Syntaxin 4 mRNA is expressed in selective tissues including rat skeletal muscle, although it has not been studied at the protein level in any cell type. Therefore, we generated an affinity-purified antibody against syntaxin 4 to demonstrate that this 36 kDa protein is expressed in rat skeletal muscle and L6 muscle cells in culture. The content of the syntaxin 4 protein increased by 1.9-fold during differentiation of L6 myoblasts into myotubes. By subcellular fractionation the protein was mainly recovered in plasma membrane-enriched fractions of both red and white skeletal muscles and L6 myotubes. Coupled to the recent detection of vesicle associated membrane protein-2 and cellubrevin in skeletal muscle, syntaxin 4 may play a role in membrane traffic in this tissue.

Animals↗
PubMed1997

Interaction of HPC-1/syntaxin 1A with the cytoskeletal protein, tubulin.

It is believed that HPC-1/syntaxin 1A regulates the intracellular membrane transport. We found a possible tubulin binding motif like sequence in residues 89 approximately 106 of HPC-1/syntaxin 1A. To determine whether or not HPC-1/syntaxin 1A binds to tubulin, we performed in vitro binding studies. We showed that both the rat brain and recombinant HPC-1/syntaxin 1A bound to tubulin in vitro. Competition experiments with synthetic peptides revealed that HPC-1/syntaxin 1A bound to tubulin at residues 89 approximately 106 which were supposed to constitute the tubulin binding consensus sequence.

Amino Acid Sequence↗
PubMed1999

Three splicing variants of tomosyn and identification of their syntaxin-binding region.

We have recently isolated a neural tissue-specific syntaxin-1-binding protein, named tomosyn, which is capable of dissociating Munc18/n-Sec1/rbSec1 from syntaxin-1 to form a 10S tomosyn complex, an intermediate complex converted to the 7S SNARE complex. We isolated here two splicing variants of tomosyn: one had 36 amino acids (aa) insertion and another had 17 aa deletion. We named original one m-tomosyn, big one b-tomosyn, and small one s-tomosyn. s-Tomosyn as well as m-tomosyn was mainly expressed in brain whereas b-tomosyn was ubiquitously expressed. All the isoforms bound to syntaxin-1, but not to syntaxin-2, -3, or -4, and had a region highly homologous to VAMP, another syntaxin-binding protein. This region was necessary but not sufficient for high-affinity binding of tomosyn to syntaxin-1.

Alternative Splicing↗
PubMed1999

Molecular cloning, expression analysis, and chromosomal localization of human syntaxin 8 (STX8).

We report the cloning of a cDNA encoding human syntaxin 8 (STX8), using the regulator (R) domain of the cystic fibrosis transmembrane conductance regulator (CFTR) as a bait to screen a human fetal lung cDNA library by the yeast two-hybrid system. This gene was found broadly transcribed and its mRNA size is about 1.3 kb. The STX8 gene maps to chromosomal band 17p12 and it encodes a 236-amino-acid protein. Syntaxin 8 contains in its C-terminal half a coiled-coil domain found highly conserved in the t-SNARE (SNAP receptor on target membrane) superfamily of proteins, which are involved in vesicular trafficking and docking. In syntaxin 8, a C-terminal hydrophobic domain may constitute a transmembrane anchor. It was recently shown that CFTR-mediated chloride currents can be regulated by syntaxin 1A, a t-SNARE family member, through direct protein-protein interaction. This raises the possibility that syntaxin 8 may also be involved in such regulations.

Amino Acid Sequence↗
PubMed2000

Molecular mechanisms of platelet exocytosis: requirements for alpha-granule release.

Platelets function by secreting components necessary for primary clot formation. This report describes an in vitro assay that measures alpha-granule secretion. Using permeabilized platelets, it is possible to recreate Ca(2+)-stimulated release of platelet factor 4 (PF4) that is ATP- and temperature-dependent. Though other divalent cations can replace Ca(2+) (i.e., Sr(2+), Mn(2+), Zn(2+)), there is no effect of Ba(2+). Analysis by electron microscopy indicates that the in vitro assay also mimics the cytoskeletal rearrangements and granule centralization that occurs upon platelet activation in vivo. Antibody inhibition studies show that PF4 release requires the general membrane fusion protein N-ethylmaleimide-sensitive factor (NSF) and well as the target membrane SNAP receptors (t-SNAREs), syntaxin 2, 4, and SNAP-23. As shown by electron microscopy, the anti-t-SNARE antibodies block granule to target membrane fusion. This finding is unique in that it is the first report of a role for two syntaxins in the same exocytosis event.

Adenosine Triphosphate↗
PubMed2001

VAP-A binds promiscuously to both v- and tSNAREs.

Proteins that bind to SNAREs may regulate their function. One such protein, VAP-33, was first discovered in Aplysia californica and has two mammalian homologues, VAP-A and VAP-B. VAP-A has been implicated in vesicle targeting to the plasma membrane based on its location in polarized cells and its ability to bind VAMP in vitro. Here, we demonstrate that VAP-A is a widely expressed resident of the ER/Golgi intermediate compartment in COS-7 cells. Moreover, we demonstrate that VAMP-binding and VAP-dimerization require both the N- and C-terminal domains of VAP-A and also that VAP-A binds to a wide range of SNAREs and fusion-related proteins including syntaxin 1A, rbet1, rsec22, alphaSNAP, and NSF. Together, these results suggest that VAP-A is not a regulator of a specific VAMP, but rather may play a more general role in SNARE-mediated vesicle traffic between the ER and Golgi in nonpolarized cells.

Animals↗
PubMed2000

The t-SNARE syntaxin is sufficient for spontaneous fusion of synaptic vesicles to planar membranes.

Vesicular trafficking and exocytosis are directed by the complementary interaction of membrane proteins that together form the SNARE complex. This complex is composed of proteins in the vesicle membrane (v-SNAREs) that intertwine with proteins of the target membrane (t-SNAREs). Here we show that modified synaptic vesicles (mSV), containing v-SNAREs, spontaneously fuse to planar membranes containing the t-SNARE, syntaxin 1A. Fusion was Ca(2+)-independent and did not occur with vesicles lacking v-SNAREs. Therefore, syntaxin alone forms a functional fusion complex with v-SNAREs. Our functional fusion assay uses synaptic vesicles that are modified, so each fusion event results in an observable transient current. The mSV do not fuse with protein-free membranes. Additionally, artificial vesicles lacking v-SNAREs do not fuse with membranes containing syntaxin. This technique can be adapted to measure fusion in other SNARE systems and should enable the identification of proteins critical to vesicle-membrane fusion. This will further our understanding of exocytosis and may improve targeting and delivery of therapeutic agents packaged in vesicles.

Animals↗
PubMed1995

Rat HPC-1/syntaxin 1A and syntaxin 1B interrupt intracellular membrane transport and inhibit secretion of the extracellular matrix in embryonic cells of an amphibian.

HPC-1/syntaxin 1A and syntaxin 1B are proteins that have been implicated in the docking and/or fusion of synaptic vesicles to the presynaptic plasma membrane in neural cells. Capped RNAs (cRNAs) for rat HPC-1 and syntaxin 1B were injected into embryonic cells of an amphibian, the Japanese newt. The effects of the proteins translated from the injected cRNAs on intracellular membrane transport and secretion of the extracellular matrix (ECM) were then investigated. Immunoblotting and immunoelectron microscopy showed that the HPC-1 synthesized in the embryonic cells was localized on the membranes of Golgi complexes and vacuoles and on the plasma membrane. Electron microscopy revealed the morphological deformation of Golgi complexes, an appearance of large number of vacuoles, and the disappearance of the ECM from the cell surface in the cRNA-injected embryos. The results showed that HPC-1 and syntaxin 1B interrupt the pathways of intracellular membrane transport and inhibit the secretion of ECM by amphibian embryonic cells. Similar mechanisms may be involved in regulation of the secretory process of synaptic vesicles in mammalian neural cells and in regulation of intracellular membrane transport and constitutive secretion of ECM in amphibian embryonic cells.

Animals↗
PubMed1996

Inductive influences of epimorphin on endothelial cells in vitro.

Epimorphin is known as a mesenchymal factor involved in epithelial morphogenesis. This protein has, however, a curious nature in that only certain of its molecules are transported to extracellular regions after having undergone complex conformational changes. In the present study, we generated an N-terminally modified recombinant epimorphin fragment as a substitute for the extracellular epimorphin and examined n detail how this polypeptide affects cellular behavior in a model cell system. As immunohistochemical studies revealed that epimorphin is abundant in regions close to endothelial cells in venulae, we chose endothelial cells as the model cell and investigated the influence of this polypeptide on their cellular behavior in vitro. The recombinant epimorphin guided the endothelial cells to align themselves in tandem and to present a branched morphology in the three-dimensional culture system. We also discovered that the endothelial cells were induced to secrete several cytokines, including those involved in angiogenesis, and were suppressed in terms of proliferation by this molecule. These results suggest that epimorphin has a regulatory role in the activation of endothelial cells and is active in supporting the resulting cellular arrangement.

Animals↗
PubMed1996

The epimorphin gene is highly conserved among humans, mice, and rats and maps to human chromosome 7, mouse chromosome 5, and rat chromosome 12.

A genomic DNA fragment containing the rat epimorphin gene sequence was cloned from a rat DNA cosmid library using a mouse epimorphin cDNA probe. Within the cosmid insert, nine epimorphin exons were identified and sequenced. The predicted amino acid sequence of the rat epimorphin protein exhibited 96 and 86% identity with the mouse and human epimorphin proteins, respectively. Consistent with the developmentally related expression pattern of the mouse epimorphin gene, transcripts of the rat epimorphin gene were detected in 17-day postfertilization rat embryos. The gene, designated Epim, was assigned to rat chromosome 12 by somatic cell hybrid analysis and localized to 12q16 by fluorescence in situ hybridization. The mouse and human homologs of this gene were localized on mouse chromosome 5 and human chromosome 7 by linkage analysis and chromosomal in situ hybridization, respectively.

Amino Acid Sequence↗
PubMed1997

Mapping of the human HPC-1/syntaxin 1A gene (STX1A) to chromosome 7 band q11.2.

We previously described the cDNA sequence of HPC-1/syntaxin 1A (HGMW-approved symbol STX1A) from rat and bovine brains. HPC-1/syntaxin 1A belongs to the syntaxin family and is apparently involved in intracellular membrane transport and the exocytosis of neurotransmitters. In this study, we isolated the cDNA and the genomic DNA clone for human HPC-1/syntaxin 1A and carried out gene mapping. Polymerase chain reaction analysis of human/rodent somatic cell hybrid panels and fluorescence in situ hybridization analysis using a genomic DNA clone provided evidence that the gene for human HPC-1/syntaxin 1A maps to chromosome region 7q11.2.

Animals↗
PubMed1999

Expression analysis and protein localization of the human HPC-1/syntaxin 1A, a gene deleted in Williams syndrome.

The HPC-1/syntaxin 1A (STX1A) gene maps to the Williams syndrome (WS) commonly deleted region on chromosome 7q11.23 and encodes a protein implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. To assess the potential role of STX1A in the WS phenotype, we carried out expression studies at the RNA and protein levels, in fetal and adult human tissues. RNA in situ hybridization on human embryo sections showed strong STX1A expression in spinal cord and ganglia. However, in adulthood, this gene was preferentially expressed in brain, as shown by Northern blot and RT-PCR experiments. Marked expression levels were observed in cerebellum and cerebral cortex. The STX1A protein was prevalently distributed in the molecular layer of the cerebellar cortex. A qualitative and quantitative analysis using a specific anti-STX1A antibody did not disclose any significant difference among frontal, temporal, and occipital poles of the human adult cortex in the two hemispheres. This is the first study focused on STX1A expression in humans. Our results indicate that this gene is strongly expressed in cerebral areas involved in cognitive process, supporting a likely role in the neurological symptoms of WS.

Antigens, Surface↗
PubMed2002

Ocsyn, a novel syntaxin-interacting protein enriched in the subapical region of inner hair cells.

Sensory (hair) cells of the inner ear contain two specialized areas of membrane delivery. The first, located at the cell base, is the afferent synapse where rapid delivery of synaptic vesicles is required to convey information about auditory signals with exceedingly high temporal precision. The second area is at the apex. To accommodate the continuous movement of stereocilia and facilitate their repair, recycling of membrane components is required. Intense vesicular traffic is restricted to a narrow band of cytoplasm around the cuticular plate, which anchors stereocilia. Our previous analyses showed that SNARE proteins (syntaxin 1A/SNAP25/VAMP1) are concentrated at both poles of hair cells, consistent with their involvement in membrane delivery at both locations. To investigate further the molecules involved in membrane delivery at these two sites, we constructed a two-hybrid library of the organ of Corti and probed it with syntaxin 1A. Here we report the cloning of a novel syntaxin-binding protein that is concentrated in a previously uncharacterized organelle at the apex of inner hair cells.

Animals↗
PubMed2002

Alternate splicing in the cytosolic II-III loop and the carboxy terminus of human E-type voltage-gated Ca(2+) channels: electrophysiological characterization of isoforms.

There is growing evidence that Ca(v)2.3 (alpha1E, E-type) transcripts may encode the ion-conducting subunit of a subclass of R-type Ca(2+) channels, a heterogeneous group of channels by definition resistant to blockers of L-, N-, and P/Q-type Ca(2+) channels. To understand whether splice variation of Ca(v)2.3 contributes to the divergence of R-type channels, individual variants of Ca(v)2.3 were constructed and expressed in HEK-293 cells. With Ba(2+) as charge carrier, the tested biophysical properties were similar. In Ca(2+), the inactivation time course was slower and the recovery from short-term inactivation was faster; however, this occurred only in variants containing a 19-amino-acid-long insertion, which is typical for neuronal Ca(v)2.3 Ca(2+) channel subunits. This different Ca(2+) sensitivity is not responsible for the major differences between various R-type channels, and future studies might clarify its importance for in vivo synaptic or dendritic integration and the reasons for its loss in endocrine Ca(v)2.3 splice variants.

Action Potentials↗