title: Syntaxin 1B, but not syntaxin 1A, is necessary for the regulation of synaptic vesicle exocytosis and of the readily releasable pool at central synapses.
abstract: Two syntaxin 1 (STX1) isoforms, HPC-1/STX1A and STX1B, are coexpressed in neurons and function as neuronal target membrane (t)-SNAREs. However, little is known about their functional differences in synaptic transmission. STX1A null mutant mice develop normally and do not show abnormalities in fast synaptic transmission, but monoaminergic transmissions are impaired. In the present study, we found that STX1B null mutant mice died within 2 weeks of birth. To examine functional differences between STX1A and 1B, we analyzed the presynaptic properties of glutamatergic and GABAergic synapses in STX1B null mutant and STX1A/1B double null mutant mice. We found that the frequency of spontaneous quantal release was lower and the paired-pulse ratio of evoked postsynaptic currents was significantly greater in glutamatergic and GABAergic synapses of STX1B null neurons. Deletion of STX1B also accelerated synaptic vesicle turnover in glutamatergic synapses and decreased the size of the readily releasable pool in glutamatergic and GABAergic synapses. Moreover, STX1A/1B double null neurons showed reduced and asynchronous evoked synaptic vesicle release in glutamatergic and GABAergic synapses. Our results suggest that although STX1A and 1B share a basic function as neuronal t-SNAREs, STX1B but not STX1A is necessary for the regulation of spontaneous and evoked synaptic vesicle exocytosis in fast transmission.
authors.affiliation: Department of Cell Physiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Mishima
authors.affiliation: Department of Cell Physiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Department of Cell Physiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Sanada
authors.affiliation: Radio Isotope Laboratory, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Kofuji
authors.affiliation: Department of Anatomy, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Kanai-Azuma
authors.affiliation: Department of Cell Physiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Kimio
authors.initials: K
authors.lastname: Akagawa
mesh_terms: D000818:Animals; D005071:Evoked Potentials / Q000502:physiology; D005089:Exocytosis / Q000502:physiology*; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism; D050827:Syntaxin 1 / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C494214:Stx1a protein, mouse; D050827:Syntaxin 1; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid