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Protein degradation and modification by the conserved ubiquitination pathway has emerged as a key cellular regulatory mechanism during nervous system development and function (Kwabe and Brose, 2011). The anaphase promoting complex\/cyclosome (APC\/C) is a multi\u2010subunit ubiquitin ligase complex primarily characterized for its role in the regulation of mitosis (Peters, 2002). In recent years, a role for APC\/C in nervous system development and function has been rapidly emerging (Stegmuller and Bonni, 2005; Li et al., 2008). In the mammalian central nervous system the activator subunit, APC\/C\u2010Cdh1, has been shown to be a regulator of axon growth and dendrite morphogenesis (Konishi et al., 2004). In the Drosophila peripheral nervous system (PNS), APC2, a ligase subunit of the APC\/C complex has been shown to regulate synaptic bouton size and activity (van Roessel et al., 2004). To investigate the role of APC\/C\u2010Cdh1 at the synapse we examined loss\u2010of\u2010function mutants of Rap\/Fzr (Retina aberrant in pattern\/Fizzy related), a Drosophila homolog of the mammalian Cdh1 during the development of the larval neuromuscular junction in Drosophila. Our cell biological, ultrastructural, electrophysiological, and behavioral data showed that <jats:italic>rap<\/jats:italic>\/<jats:italic>fzr<\/jats:italic> loss\u2010of\u2010function mutations lead to changes in synaptic structure and function as well as locomotion defects. Data presented here show changes in size and morphology of synaptic boutons, and, muscle tissue organization. Electrophysiological experiments show that loss\u2010of\u2010function mutants exhibit increased frequency of spontaneous miniature synaptic potentials, indicating a higher rate of spontaneous synaptic vesicle fusion events. In addition, larval locomotion and peristaltic movement were also impaired. These findings suggest a role for Drosophila APC\/C\u2010Cdh1 mediated ubiquitination in regulating synaptic morphology, function and integrity of muscle structure in the peripheral nervous system.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2013.07.002","type":"journal-article","created":{"date-parts":[[2013,8,7]],"date-time":"2013-08-07T01:58:31Z","timestamp":1375840711000},"page":"624-633","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Drosophila\u2010Cdh1 (Rap\/Fzr) a regulatory subunit of APC\/C is required for synaptic morphology, synaptic transmission and locomotion"],"prefix":"10.1002","volume":"31","author":[{"given":"Alexandria","family":"Wise","sequence":"first","affiliation":[{"name":"Department of Biology City College of New York and The Graduate Center of CUNY New York NY 10031 United States"},{"name":"Department of Pathology and Cell Biology Columbia University 630 West 168th Street New York NY 10032 United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Schatoff","sequence":"additional","affiliation":[{"name":"Department of Biology City College of New York and The Graduate Center of CUNY New York NY 10031 United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Flores","sequence":"additional","affiliation":[{"name":"Department of Biology City College of New York and The Graduate Center of CUNY New York NY 10031 United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shao\u2010Ying","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Biology York College City University of New York NY 11415 United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Biology University of Iowa Iowa City IA 52242\u20101324 United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun\u2010Fang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biology University of Iowa Iowa City IA 52242\u20101324 United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadmiri","family":"Venkatesh","sequence":"additional","affiliation":[{"name":"Department of Biology City College of New York and The Graduate Center of CUNY New York NY 10031 United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,8,6]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.480240803"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.1093\/emboj\/cdf452","article-title":"Timing of APC\/C substrate degradation is determined by fzy\/fzr specificity of destruction boxes","volume":"21","author":"Brandeis A.Z.","year":"2002","journal-title":"EMBO Journal"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00749-3"},{"issue":"5","key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1152\/jn.01115.2003","article-title":"Electrophysiological and morphological characterization of identified motor neurons in the Drosophila third instar larva central nervous system","volume":"91","author":"Choi J.C.","year":"2004","journal-title":"J. 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