Tomosyn: a syntaxin-1-binding protein that forms a novel complex in the neurotransmitter release process.
Syntaxin-1 is a component of the synaptic vesicle docking and/or membrane fusion soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) complex (7S and 20S complexes) in nerve terminals. Syntaxin-1 also forms a heterodimer with Munc18/n-Sec1/rbSec1 in a complex that is distinct from the 7S and 20S complexes. In this report, we identify a novel syntaxin-1-binding protein, tomosyn, that is capable of dissociating Munc18 from syntaxin-1 and forming a novel 10S complex with syntaxin-1, soluble N-etyhlmaleimide-sensitive factor attachment (SNAP) 25, and synaptotagmin. The 130 kDa isoform of tomosyn is specifically expressed in brain, where its distribution partly overlaps with that of syntaxin-1 in nerve terminals. High level expression of either syntaxin-1 or tomosyn results in a specific reduction in Ca2+-dependent exocytosis from PC12 cells. These results suggest that tomosyn is an important component in the neurotransmitter release process where it may stimulate SNARE complex formation.
Fujita
Y
Y
Department of Molecular Biology and Biochemistry, Osaka University Medical School, Suita, Japan.
Shirataki
H
H
Sakisaka
T
T
Asakura
T
T
Ohya
T
T
Kotani
H
H
Yokoyama
S
S
Nishioka
H
H
Matsuura
Y
Y
Mizoguchi
A
A
Scheller
R H
RH
Takai
Y
Y
D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry / Q000378:metabolism*; D015153:Blotting, Western; D001923:Brain Chemistry; D019556:COS Cells / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005089:Exocytosis / Q000502:physiology; D007536:Isomerism; D008969:Molecular Sequence Data; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D016716:PC12 Cells; D011485:Protein Binding / Q000502:physiology; D050683:R-SNARE Proteins; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology*; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins
D000954:Antigens, Surface; D002352:Carrier Proteins; D018076:DNA, Complementary; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D050683:R-SNARE Proteins; C494213:Stx1a protein, rat; C484769:Stxbp5 protein, rat; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins; D002118:Calcium