Search PubMed⌕ Search

PubMed · 9785471

SNAP-25.

Abstract

SNAP-25 belongs to a family of evolutionarily conserved proteins whose members are essential for exocytosis. Neurons and neuroendocrine cells differentially express two SNAP-25 isoforms in a developmentally regulated manner, and related homologues have been detected in most eukaryotic cells. SNAP-25 is localised on the cytoplasmic face of the plasma membrane and on secretory vesicles. It forms a stable ternary complex with two other exocytotic proteins: syntaxin and the synaptic vesicle protein synaptobrevin. A cytosolic ATPase dissociates this complex during priming of the exocytotic apparatus. Subsequent reassembly is promoted by SNAP-25 and may drive Ca(2+)-triggered vesicle-plasma membrane fusion. A mutant mouse that lacks the SNAP-25 gene is defective in neuronal dopamine signalling and exhibits similar behaviour as sufferers from hyperactivity disorders. Use of this animal model thus provides a promising avenue for the development of therapeutic treatments. Additionally, SNAP-25-based peptides that mimic the effect of botulinum neurotoxin A may be used for the treatment of involuntary muscle spasms.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

A Hodel. 1998. SNAP-25.. https://doi.org/10.1016/s1357-2725(98)00079-x

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Chimeric structural isomer fragments as cost-efficient internal standards for amino acid quantification by mass spectrometry.

Amino acid (AA) profiles from body fluids such as blood and urine are clinical indicators for diagnosing metabolic and hepatic diseases. Current quantitative methods, such as liquid chromatography-mass spectrometry (LC-MS) with isotopically labelled internal standards (ISs), are costly and technically demanding. This study proposes a cost-efficient alternative using structural isomers as ISs in a direct liquid infusion (DLI) tandem mass spectrometry (MS/MS) approach. The method leverages chimeric spectra and fragment intensity ratios to quantify AAs, demonstrating high linearity and precision even with a 3D ion trap mass analyser. This approach offers a viable strategy for AA quantification in preventive medicine, particularly for screening metabolic diseases such as phenylketonuria, diabetes, and liver dysfunction.

Amino Acids↗

Characterization of proteoglycans of human placenta and identification of unique chondroitin sulfate proteoglycans of the intervillous spaces that mediate the adherence of Plasmodium falciparum-infected erythrocytes to the placenta.

In pregnant women infected with Plasmodium falciparum, the infected red blood cells (IRBCs) selectively accumulate in the intervillous spaces of placenta, leading to poor fetal outcome and severe health complications in the mother. Although chondroitin 4-sulfate is known to mediate IRBC adherence to placenta, the natural receptor has not been identified. In the present study, the chondroitin sulfate proteoglycans (CSPGs) of human placenta were purified and structurally characterized, and adherence of IRBCs to these CSPGs investigated. The data indicate that the placenta contains three distinct types of CSPGs: significant quantities of uniquely low sulfated, extracellular CSPGs localized in the intervillous spaces, minor amounts of two cell-associated CSPGs, and major amounts of dermatan sulfate-like CSPGs of the fibrous tissue. Of the various CSPGs isolated from the placenta, the low sulfated CSPGs of the intervillous spaces most efficiently bind IRBCs. Based on IRBC adherence capacities and localization patterns of various CSPGs, we conclude that the CSPGs of the intervillous spaces are the receptors for placental IRBC adherence. The identification and characterization of these CSPGs provide a valuable tool for understanding the precise molecular interactions involved in placental IRBC adherence and for the development of therapeutic strategies for maternal malaria. In the accompanying paper (Alkhalil, A., Achur, R. N., Valiyaveettil, M., Ockenhouse, C. F., and Gowda, D. C. (2000) J. Biol. Chem. 275, 40357-40364), we report the structural requirements for the IRBC adherence.

Amino Acids↗

Protein phosphatase 2A is associated with class C L-type calcium channels (Cav1.2) and antagonizes channel phosphorylation by cAMP-dependent protein kinase.

Phosphorylation by cAMP-dependent protein kinase (PKA) regulates a vast number of cellular functions. An important target for PKA in brain and heart is the class C L-type Ca(2+) channel (Ca(v)1.2). PKA phosphorylates serine 1928 in the central, pore-forming alpha(1C) subunit of this channel. Regulation of channel activity by PKA requires a proper balance between phosphorylation and dephosphorylation. For fast and specific signaling, PKA is recruited to this channel by an protein kinase A anchor protein (Davare, M. A., Dong, F., Rubin, C. S., and Hell, J. W. (1999) J. Biol. Chem. 274, 30280-30287). A phosphatase may be associated with the channel to effectively balance serine 1928 phosphorylation by channel-bound PKA. Dephosphorylation of this site is mediated by a serine/threonine phosphatase that is inhibited by okadaic acid and microcystin. We show that immunoprecipitation of the channel complex from rat brain results in coprecipitation of PP2A. Stoichiometric analysis indicates that about 80% of the channel complexes contain PP2A. PP2A directly and stably binds to the C-terminal 557 amino acids of alpha(1C). This interaction does not depend on serine 1928 phosphorylation and is not altered by PP2A catalytic site inhibitors. These results indicate that the PP2A-alpha(1C) interaction constitutively recruits PP2A to the channel complex rather than being a transient substrate-catalytic site interaction. Functional assays with the immunoisolated class C channel complex showed that channel-associated PP2A effectively reverses serine 1928 phosphorylation by endogenous PKA. Our findings demonstrate that both PKA and PP2A are integral components of the class C L-type Ca(2+) channel that determine the phosphorylation level of serine 1928 and thereby channel activity.

Amino Acids↗