Molecular mechanism of rectification at identified electrical synapses in the Drosophila giant fiber system.
Electrical synapses are neuronal gap junctions that mediate fast transmission in many neural circuits. The structural proteins of gap junctions are the products of two multigene families. Connexins are unique to chordates; innexins/pannexins encode gap-junction proteins in prechordates and chordates. A concentric array of six protein subunits constitutes a hemichannel; electrical synapses result from the docking of hemichannels in pre- and postsynaptic neurons. Some electrical synapses are bidirectional; others are rectifying junctions that preferentially transmit depolarizing current anterogradely. The phenomenon of rectification was first described five decades ago, but the molecular mechanism has not been elucidated. Here, we demonstrate that putative rectifying electrical synapses in the Drosophila Giant Fiber System are assembled from two products of the innexin gene shaking-B. Shaking-B(Neural+16) is required presynaptically in the Giant Fiber to couple this cell to its postsynaptic targets that express Shaking-B(Lethal). When expressed in vitro in neighboring cells, Shaking-B(Neural+16) and Shaking-B(Lethal) form heterotypic channels that are asymmetrically gated by voltage and exhibit classical rectification. These data provide the most definitive evidence to date that rectification is achieved by differential regulation of the pre- and postsynaptic elements of structurally asymmetric junctions.
Phelan
Pauline
P
Department of Biosciences, University of Kent, Canterbury, UK. p.phelan@kent.ac.uk
Goulding
L Ann
LA
Tam
Jennifer L Y
JL
Allen
Marcus J
MJ
Dawber
Rebecca J
RJ
Davies
Jane A
JA
Bacon
Jonathan P
JP
D000818:Animals; D030801:Animals, Genetically Modified; D017630:Connexins / Q000235:genetics / Q000502:physiology; D004330:Drosophila / Q000033:anatomy & histology / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology; D054351:Electrical Synapses / Q000502:physiology*; D055724:Electrophysiological Phenomena; D005260:Female; D018390:Gene Targeting; D017344:Genes, Insect; D015640:Ion Channel Gating; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000502:physiology; D009865:Oocytes / Q000378:metabolism; D010641:Phenotype; D017729:Presynaptic Terminals / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014981:Xenopus
D017630:Connexins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C079324:shakB protein, Drosophila