title: Synaptogyrin-dependent modulation of synaptic neurotransmission in Caenorhabditis elegans.
abstract: The tetraspan membrane proteins of the synaptogyrin and synaptophysin type are abundant and evolutionary conserved synaptic vesicle membrane proteins whose functions are poorly defined. Their depletion does not interfere with proper neuronal development and basic neuronal function. In the search for their function we use the genetic model organism Caenorhabditis elegans in which, in contrast to vertebrates, the synaptogyrin but not the synaptophysin orthologue is predominant in neurons. Employing fluorescent reporter constructs we find that synaptogyrin is expressed in all GABAergic neurons and most, though not all other neurons. Subjecting animals either lacking or overexpressing synaptogyrin to the epileptogenic GABA antagonist pentylenetetrazole reveals increased sensitivity in comparison to the wild-type. Detailed analyses further uncover mildly altered motility, slightly reduced sensitivity to the acetylcholine esterase inhibitor aldicarb and decreased recruitment of synaptobrevin but not of RAB-3 to synapses. Furthermore, synthetic phenotypes are observed with mutants of the synaptic vesicle recycling machinery, notably with synaptotagmin, synaptojanin and endophilin rather than with mutants involved in clathrin-dependent endocytosis. Taken together, these observations assign a distinct modulatory and redundant neuronal function to synaptogyrin.
authors.affiliation: Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Abraham
authors.forename: L
authors.initials: L
authors.lastname: Bai
authors.forename: R E
authors.initials: RE
authors.lastname: Leube
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010433:Pentylenetetrazole / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D050683:R-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D062805:Synaptogyrins; D050857:Synaptotagmins / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D018756:GABA Antagonists; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D062805:Synaptogyrins; D050857:Synaptotagmins; D005680:gamma-Aminobutyric Acid; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases; D010433:Pentylenetetrazole