title: Requirement for the synaptic protein interaction site for reconstitution of synaptic transmission by P/Q-type calcium channels.
abstract: Ca(v)2.1 channels, which conduct P/Q-type Ca(2+) currents, were expressed in superior cervical ganglion neurons in cell culture, and neurotransmission initiated by these exogenously expressed Ca(2+) channels was measured. Deletions in the synaptic protein interaction (synprint) site in the intracellular loop between domains II and III of Ca(v)2.1 channels reduced their effectiveness in synaptic transmission. Surprisingly, this effect was correlated with loss of presynaptic localization of the exogenously expressed channels. Ca(v)1.2 channels, which conduct L-type Ca(2+) currents, are ineffective in supporting synaptic transmission, but substitution of the synprint site from Ca(v)2.1 channels in Ca(v)1.2 was sufficient to establish synaptic transmission initiated by L-type Ca(2+) currents through the exogenous Ca(v)1.2 channels. Substitution of the synprint site from Ca(v)2.2 channels, which conduct N-type Ca(2+) currents, was even more effective than Ca(v)2.1. Our results show that localization and function of exogenous Ca(2+) channels in nerve terminals of superior cervical ganglion neurons require a functional synprint site and suggest that binding of soluble NSF attachment protein receptor (SNARE) proteins to the synprint site is a necessary permissive event for nerve terminal localization of presynaptic Ca(2+) channels.
authors.affiliation: Department of Physiology, Tokyo Medical University, Tokyo 160-8402, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Mochida
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Westenbroek
authors.forename: Charles T
authors.initials: CT
authors.lastname: Yokoyama
authors.forename: Huijun
authors.initials: H
authors.lastname: Zhong
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Myers
authors.forename: Todd
authors.initials: T
authors.lastname: Scheuer
authors.forename: Kanako
authors.initials: K
authors.lastname: Itoh
authors.forename: William A
authors.initials: WA
authors.lastname: Catterall
mesh_terms: D001665:Binding Sites; D020746:Calcium Channels, L-Type / Q000737:chemistry* / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004594:Electrophysiology; D005091:Exons; D017353:Gene Deletion; D005822:Genetic Vectors; D015151:Immunoblotting; D007438:Introns; D008565:Membrane Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D050600:SNARE Proteins; D013569:Synapses / Q000502:physiology*; D013997:Time Factors; D014162:Transfection; D033921:Vesicular Transport Proteins
chemical_list: D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D018076:DNA, Complementary; D008565:Membrane Proteins; D020033:Protein Isoforms; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; C419385:L-type calcium channel alpha(1C)