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J Pevsner

Publications and source records attributed to J Pevsner.

At least 19 recordsLinked to original sources
PubMed1996

The role of Sec1p-related proteins in vesicle trafficking in the nerve terminal.

Vesicle trafficking at multiple stages of the secretory pathway depends on a family of soluble proteins related to yeast Sec1p. In yeast, this family consists of four members: the late-acting Sec1p that is required for vesicular transport between the Golgi apparatus and the cell surface; Vps33p and Vps45p which are required for trafficking between the Golgi complex and the lysosome-like vacuole; and Sly1p that is essential for trafficking between the endoplasmic reticulum and the Golgi apparatus. In mammalian systems, homologues of these proteins have been identified. In particular, a neural-specific Sec1p homologue (n-sec1/Munc-18) binds the plasma membrane protein syntaxin and may regulate synaptic vesicle docking. The Sec1p family of proteins is essential for vesicle trafficking in both regulated and constitutive trafficking pathways, and n-sec1 is critical in the regulated release of neurotransmitter from the nerve terminal.

Animals↗
PubMed1996

The three-dimensional structure of bovine odorant binding protein and its mechanism of odor recognition.

Odorant binding protein (OBP) is the major odorant binding component of mammalian nasal mucosa. The two structures of bovine OBP reported in this paper (one crystallized as purified and one soaked in the presence of a selenium-containing odorant) show that: (i) the OBP dimer is composed of two compact domains related by an approximate two-fold axis of symmetry; (ii) between residues 122 and 123 the polypeptide chains cross from one domain to the other such that each domain is formed by residues from both monomers; (iii) purified OBP already contains two bound odorant molecules (one per monomer)-odorant binding occurs by replacement of these molecules with the added odorant; and (iv) the structure of the odorant binding site can explain OBP's extraordinarily broad odorant specificity.

Alpha-Globulins↗
PubMed1994

Two rat homologs of clathrin-associated adaptor proteins.

A cDNA clone predicted to encode a 46,757-Da protein was isolated from a library derived from the electric lobe of the ray Discopyge ommata. Two rat homologs, p47A and p47B, were subsequently isolated. These three proteins share approx. 80% amino acid (aa) identity to each other and have 27-30% aa identity to rat AP50 and mouse AP47, the medium-chain subunits of adaptor complexes associated with clathrin-coated vesicles. These complexes are involved in receptor-mediated pathways of intracellular transport. Rat p47A mRNA is expressed in all tissues examined, including brain, heart, kidney, liver, lung, muscle and spinal cord. Rat p47B mRNA is detected exclusively in brain and spinal cord, and may participate in nervous system-specific functions such as biogenesis or recycling of synaptic vesicles.

Amino Acid Sequence↗
PubMed1994

n-Sec1: a neural-specific syntaxin-binding protein.

We have identified n-Sec1, a rat brain homolog of the yeast Sec1p protein that participates in the constitutive secretory pathway between the Golgi apparatus and the plasma membrane. The rat brain cDNA is predicted to encode a 68-kDa protein with 65% amino acid identity to Drosophila rop, 59% identity to Caenorhabditis elegans unc-18, and 27% identity to Saccharomyces cerevisiae Sec1p. By RNA blot analysis, n-Sec1 mRNA expression is neural-specific. An anti-peptide antiserum directed against the n-Sec1 carboxyl terminus detects a 68-kDa protein in rat brain cytosol and membranes, but not in peripheral tissues. In the presence of syntaxin 1a, a plasma membrane protein implicated in synaptic vesicle docking, n-Sec1 becomes membrane-associated. n-Sec1 binds to syntaxin 1a, 2, and 3 fusion proteins coupled to agarose beads, but not to syntaxin 4 fusion protein or beads coupled to a variety of other proteins. These findings indicate that n-Sec1 is a neural-specific, syntaxin-binding protein that may participate in the regulation of synaptic vesicle docking and fusion.

Amino Acid Sequence↗
PubMed1994

Specificity and regulation of a synaptic vesicle docking complex.

Synaptic vesicles are proposed to dock at the presynaptic plasma membrane through the interaction of two integral membrane proteins of synaptic vesicles, VAMP and synaptotagmin, and two plasma membrane proteins, syntaxin and SNAP-25. We have characterized the binding properties of these proteins and observed SNAP-25 potentiation of VAMP 2 binding to syntaxins 1a and 4 but not syntaxins 2 or 3. n-sec1, a neuron-specific syntaxin-binding protein, bound syntaxin with nanomolar affinity, forming a complex that is distinct from the previously identified 7S and 20S syntaxin-containing complexes. This suggests that syntaxin exists in at least three states: bound to n-sec1, in a 7S particle, and in a 20S particle. Recombinant n-sec1 inhibited VAMP or SNAP-25 binding to syntaxin. We propose that the specific associations of VAMP, SNAP-25, and syntaxin mediate vesicle docking and that a syntaxin/n-sec1 complex precedes and/or regulates formation of these complexes.

Amino Acid Sequence↗
PubMed1994

Mechanisms of vesicle docking and fusion: insights from the nervous system.

Upon stimulation of nerve cells, synaptic vesicles fuse with the presynaptic plasma membrane to release neurotransmitter. The biochemical pathway responsible for synaptic-vesicle docking and fusion is now being elucidated. Many of the proteins implicated in this process have homologs elsewhere in the cell. The docking and fusion mechanism discussed in this review may account for the specificity of vesicular trafficking throughout both regulated and constitutive secretory pathways.

Animals↗
PubMed1993

Association of three small GTP-binding proteins with cholinergic synaptic vesicles.

Several small (low molecular weight) GTP-binding proteins are associated with cholinergic synaptic vesicles derived from the electric organ of electric ray. Using GTP overlay techniques and direct micro sequencing we analyzed the association of small GTP-binding proteins with synaptic vesicles. Both experimental procedures revealed the specific occurrence of multiple small GTP-binding proteins with this organelle. Moreover, direct amino acid sequence analysis assigned at least three different small GTP-binding proteins, ora3, o-ral and o-rab3, to the vesicular compartment. Furthermore, the data reflect the relative abundance of these three proteins on the vesicle membrane, thereby demonstrating the predominant occurrence of o-rab3, the only exclusively synaptic vesicle specific small GTP-binding protein.

Amino Acid Sequence↗
PubMed1991

5'-nucleotidase from the electric ray electric lobe. Primary structure and relation to mammalian and procaryotic enzymes.

A cDNA encoding a 5'-nucleotidase was identified by screening a lambda gt10 cDNA library from the electric lobe of Discopyge ommata using a cDNA probe containing the complete open reading frame coding for the rat liver enzyme. Nucleotide sequence analysis defines an open reading frame of 577 amino acids, corresponding to a calculated molecular mass of 63,833 Da. The N-terminus of the mature protein, as determined by direct protein sequencing, is preceded by 29 amino acid residues comprising a signal peptide. The C-terminus contains a stretch of hydrophobic amino acids, considered to be cleaved on post-translational modification and exchanged for glycosylphosphatidylinositol as a membrane anchor. The predicted protein contains four potential N-linked glycosylation sites. Electric ray 5'-nucleotidase shares 61% amino acid identity with the enzymes from rat liver and human placenta, and about 23% with bacterial proteins possessing 5'-nucleotidase activity and also additional enzyme activities like UDP-glucose hydrolase. Polyclonal antibodies raised against 5'-nucleotidase from mammalian sources or the electric ray electric organ reveal mutual cross-reactivity. Interestingly, there are 5-7 domains highly conserved in procaryotes and vertebrates in enzymes exhibiting 5'-nucleotidase, 3'-nucleotidase or phosphodiesterase activity. 5'-nucleotidase isolated from Torpedo electric organ hydrolyzes UDP-glucose at 8% of the rate of AMP hydrolysis. The possible phylogenetic origin of vertebrate 5'-nucleotidase from multifunctional nucleotide hydrolases is discussed.

5'-Nucleotidase↗
PubMed1991

A synaptic vesicle specific GTP-binding protein from ray electric organ.

A cDNA encoding a synaptic vesicle associated GTP-binding protein was identified by screening a lambda gt11 expression library derived from the electric lobe of Discopyge ommata with polyclonal antibodies recognizing vesicle-specific proteins of Mr 25,000. Nucleotide sequence analysis defines an open reading frame of 218 amino acids. The protein belongs to the ras superfamily and shares about 75% amino acid identity with smg-25A, B and C identified in bovine brain and rab3A characterized in rat brain. Northern blot analysis revealed a 4.5 kb transcript present only in neural tissues, the highest level of expression being observed in electric lobe. Western blot analysis of total tissue homogenates derived from D. ommata detected the protein in electric organ, forebrain and to a lesser extent in electric lobe and spinal cord. No immunoreactivity was detected in non-neuronal tissues. Blotting of subcellular fractions derived from electric ray electric organ revealed that the GTP-binding protein co-purifies with synaptic vesicles. The neural specific expression and the localization to synaptic vesicles suggest a role of this protein in synaptic vesicle trafficking and targeting.

Amino Acid Sequence↗
PubMed1990

Odorant-binding protein. Characterization of ligand binding.

We have characterized the odorant binding properties of purified bovine odorant-binding protein (OBP) using as a ligand [3H]3,7-dimethyloctan-1-ol ([3H]DMO). A broad variety of odorants, including terpenes, aldehydes, esters, and musks, bind to OBP with affinities of 0.2 to 100 microM. Odorant affinities for OBP correlate most closely with their stimulation of an odorant-sensitive adenylyl cyclase as well as hydrophobicity. We also measured the kinetics of binding for the ligands, [3H]DMO and 2-isobutyl-3-[3H]methoxypyrazine. Dissociation of both is markedly accelerated in the presence of excess unlabeled ligand. Competition curves of displacers for [3H]DMO binding are shallow, and saturation binding isotherms for 3H-odorants are curvilinear. These kinetic and equilibrium binding properties suggest that OBP interactions with odorant ligands are negatively cooperative.

Animals↗
PubMed1989

Molecular mechanisms of olfaction.

Recent studies provide initial insights into molecular mechanisms of olfaction. The identification of an odorant-sensitive adenylate cyclase which responds to most odorants, affords a second messenger system following odorant interactions with receptors. Cyclic nucleotide- and odorant-gated ion channels have been demonstrated in olfactory cilia, providing signalling systems in place of or in addition to protein phosphorylation. A unique odorant-binding protein localized to nasal mucosa binds odorants in proportion to their odoriferous potencies. Molecular cloning of the isolated protein reveals it to be a member of a family of proteins that serve as carriers for small lipophilic molecules such as retinol and cholesterol. The odorant-binding protein is localized to lateral nasal glands whose secretions are atomized into the tip of the nose where the binding protein presumably interacts with odorants in the inspired air.

Animals↗
PubMed1989

Abnormal renal mobility--an indication for surgical intervention.

Movable kidney is a debated entity and therefore not diagnosed in many cases. According to our experience the diagnosis should be made much more frequent in patients who suffer from loin and/or abdominal pain which is relieved by recumbent position. Twenty-nine cases of patients who suffered from loin and/or abdominal pain and were diagnosed as suffering from abnormal renal mobility by medical history, intravenous pyelogram, angiography and dynamic scanning were operated upon with a reported high rate of relief of pain (87%; 25/29). The technique employed was the modified Deming operation.

Abdomen↗
PubMed1988

Molecular cloning of odorant-binding protein: member of a ligand carrier family.

Odorant-binding protein (OBP) is found in nasal epithelium, and it selectively binds odorants. Three complementary DNAs encoding rat odorant-binding protein have now been cloned and sequenced. One clone contains an open reading frame predicted to encode an 18,091-dalton protein. RNA blot analysis confirms the localization of OBP messenger RNA in the nasal epithelium. This OBP has 33 percent amino acid identity to alpha 2-microglobulin, a secreted plasma protein. Other members of an alpha 2-microglobulin superfamily bind and transport hydrophobic ligands. Thus, OBP probably binds and carries odorants within the nasal epithelium to putative olfactory receptors.

Amino Acid Sequence↗
PubMed1988

Odorant-binding protein and its mRNA are localized to lateral nasal gland implying a carrier function.

Odorant-binding protein selectively binds various odorants and is discretely concentrated in nasal mucosa and secretions. We have localized rat odorant-binding protein mRNA to the lateral nasal gland by in situ hybridization histochemistry and have also localized the protein to this gland by immunohistochemistry and by tritiated-odorant autoradiography. The lateral nasal gland extends a long duct toward the external nares. Odorant-binding protein, released from this duct, may transport odorants to olfactory receptor neurons.

Animals↗
PubMed1986

Odorant-binding protein: localization to nasal glands and secretions.

An odorant-binding protein (OBP) was isolated from bovine olfactory and respiratory mucosa. We have produced polyclonal antisera to this protein and report its immunohistochemical localization to mucus-secreting glands of the olfactory and respiratory mucosa. Although OBP was originally isolated as a pyrazine binding protein, both rat and bovine OBP also bind the odorants [3H]methyldihydrojasmonate and 3,7-dimethyl-octan-1-ol as well as 2-isobutyl-3-[3H]methoxypyrazine. We detect substantial odorant-binding activity attributable to OBP in secreted rat nasal mucus and tears but not in saliva, suggesting a role for OBP in transporting or concentrating odorants.

Animals↗
PubMed1985

Fetal methylazoxymethanol acetate-induced lesions cause reductions in dopamine receptor-mediated catalepsy and stereotypy.

Telencephalic hypoplasia induced by methylazoxymethanol acetate (MAM) resulted in increased activity of tyrosine hydroxylase in the striatum, indicative of a relative increase in the density of dopaminergic terminals in the remaining tissue. Administration of the dopamine receptor stimulant, apomorphine, or the receptor blocker, haloperidol, produced less stereotypy and catalepsy, respectively, in rats lesioned with methylazoxymethanol, compared to controls. These behavioral changes probably resulted from the loss of striatal perikarya and consequent decrease in nigrostriatal dopaminergic target sites caused by methylazoxymethanol.

Animals↗