SV2C is a synaptic vesicle protein with an unusually restricted localization: anatomy of a synaptic vesicle protein family

We describe here the identification and molecular characterization of a new brain protein that we named SV2C because it is homologous to the synaptic vesicle proteins SV2A and SV2B, and because it is also recognized by the monoclonal SV2 antibody that led to the initial discovery of SV2A and SV2B. S...

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Bibliographic Details
Published in:Neuroscience 1999-01, Vol.94 (4), p.1279-1290
Main Authors: Janz, R, Südhof, T.C
Format: Article
Language:English
Subjects:
Amino Acid Sequence - genetics
Animals
Antibodies
Biochemistry and metabolism
Biological and medical sciences
Blotting, Northern
Brain - metabolism
Central nervous system
Chromaffin Granules - metabolism
Cloning, Molecular
COS Cells
DNA, Complementary - genetics
Fundamental and applied biological sciences. Psychology
glycoprotein
Glycosylation
Hydrogen-Ion Concentration
Immunohistochemistry
Membrane Glycoproteins - genetics
Membrane Glycoproteins - immunology
Membrane Glycoproteins - metabolism
Molecular Conformation
Molecular Sequence Data
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - immunology
Nerve Tissue Proteins - metabolism
Peptide Fragments - chemical synthesis
Peptide Fragments - immunology
Protein Isoforms - metabolism
Subcellular Fractions - metabolism
SV2
SVOP
synaptic vesicle
Tissue Distribution
transporter
Vertebrates: nervous system and sense organs
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Summary:We describe here the identification and molecular characterization of a new brain protein that we named SV2C because it is homologous to the synaptic vesicle proteins SV2A and SV2B, and because it is also recognized by the monoclonal SV2 antibody that led to the initial discovery of SV2A and SV2B. SV2C is more closely related to SV2A (62% identity) than to SV2B (57% identity), and contains 12 transmembrane regions similar to these proteins. To characterize SV2C and compare its properties and localization with those of SV2A and SV2B, we raised an SV2C-specific antibody. Using this antibody, we show that SV2C is an N-glycosylated protein that is concentrated on small synaptic vesicles; in addition, it is found on microvesicles in adrenal chromaffin cells. We evaluated the relative localization of the three SV2 isoforms by staining rat brain sections with antibodies specific for SV2A, SV2B and SV2C. Analysis of the resulting staining patterns confirmed previous conclusions that SV2A is ubiquitously expressed in virtually all synapses. SV2B, although more restricted in distribution, was also found in a wide variety of synapses throughout the brain. In striking contrast to this general localization and to similarly wide distributions of other synaptic vesicle proteins, SV2C was observed only in few brain areas. High levels of SV2C were found primarily in phylogenetically old brain regions such as the pallidum, the substantia nigra, the midbrain, the brainstem and the olfactory bulb. SV2C was undetectable in the cerebral cortex and the hippocampus, and found at low levels in the cerebellar cortex. Our data suggest that closely related members of a synaptic vesicle protein family can either have very general (SV2A) or restricted distributions (SV2C), possibly in order to allow specialization in the regulation of the expression or of the function of these abundant synaptic vesicle proteins.
ISSN:0306-4522
1873-7544
DOI:10.1016/S0306-4522(99)00370-X