Drosophila CAKI/CMG Protein, a Homolog of Human CASK, Is Essential for Regulation of Neurotransmitter Vesicle Release

1 Departments of Human Anatomy and Physiology and 2 Biology, University of Padova, Padova, Italy; and 3 Equipe Action Thématique et Initiatíve sur Programme et Equipe: Bases Neurales du Mouvement chez la Drosophile, Neurobiologie de l’Apprendissage, de la Mémozie et de la Communication, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8620, Université Paris Sud, Orsay, France Submitted 14 September 2004; accepted in final form 27 April 2005 Vertebrate CASK is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins. CASK is present in the nervous system where it binds to neurexin, a transmembrane protein localized in the presynaptic membrane. The Drosophila homologue of CASK is CAKI or CAMGUK. CAKI is expressed in the nervous system of larvae and adult flies. In adult flies, the expression of caki is particularly evident in the visual brain regions. To elucidate the functional role of CASK, we employed a caki null mutant in the model organism Drosophila melanogaster . By means of electrophysiological methods, we analyzed, in adult flies, the spontaneous and evoked neurotransmitter release at the neuromuscular junction (NMJ) as well as the functional status of the giant fiber pathway and of the visual system. We found that in caki mutants, when synaptic activity is modified, the spontaneous neurotransmitter release of the indirect flight muscle NMJ was increased, the response of the giant fiber pathway to continuous stimulation was impaired, and electroretinographic responses to single and continuous repetitive stimuli were altered and optomotor behavior was abnormal. These results support the involvement of CAKI in neurotransmitter release and nervous system function. Address for reprint requests and other correspondence: A. Megighian, Dept. of Human Anatomy and Physiology, Section of Physiology, University of Padua, Italy Via Marzolo 3, 35131, Padova, Italy (E-mail: aram.megighian{at}unipd.it )