| Title: | Central regulation of locomotor behavior of Drosophila melanogaster depends on a CASK isoform containing CaMK-like and L27 domains |
| Author(s): | Slawson JB; Kuklin EA; Ejima A; Mukherjee K; Ostrovsky L; Griffith LC; |
| Address: | "Department of Biology, Volen Center for Complex Systems and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts 02454-9110, USA" |
| DOI: | 10.1534/genetics.110.123406 |
| ISSN/ISBN: | 1943-2631 (Electronic) 0016-6731 (Print) 0016-6731 (Linking) |
| Abstract: | "Genetic causes for disturbances of locomotor behavior can be due to muscle, peripheral neuron, or central nervous system pathologies. The Drosophila melanogaster homolog of human CASK (also known as caki or camguk) is a molecular scaffold that has been postulated to have roles in both locomotion and plasticity. These conclusions are based on studies using overlapping deficiencies that largely eliminate the entire CASK locus, but contain additional chromosomal aberrations as well. More importantly, analysis of the sequenced Drosophila genome suggests the existence of multiple protein variants from the CASK locus, further complicating the interpretation of experiments using deficiency strains. In this study, we generated small deletions within the CASK gene that eliminate gene products containing the CaMK-like and L27 domains (CASK-beta), but do not affect transcripts encoding the smaller forms (CASK-alpha), which are structurally homologous to vertebrate MPP1. These mutants have normal olfactory habituation, but exhibit a striking array of locomotor problems that includes both initiation and motor maintenance defects. Previous studies had suggested that presynaptic release defects at the neuromuscular junction in the multigene deficiency strain were the likely basis of its locomotor phenotype. The locomotor phenotype of the CASK-beta mutant, however, cannot be rescued by expression of a CASK-beta transgene in motor neurons. Expression in a subset of central neurons that does not include the ellipsoid body, a well-known pre-motor neuropil, provides complete rescue. Full-length CASK-beta, while widely expressed in the nervous system, appears to have a unique role within central circuits that control motor output" |
| Keywords: | "Animals Brain/drug effects/metabolism/physiology Chromosome Mapping Circadian Rhythm/drug effects/genetics Courtship Drosophila melanogaster/drug effects/*enzymology/genetics/*physiology Female Gene Expression Regulation, Enzymologic/drug effects Genetic;" |
| Notes: | "MedlineSlawson, Justin B Kuklin, Elena A Ejima, Aki Mukherjee, Konark Ostrovsky, Lilly Griffith, Leslie C eng F31 NS064679/NS/NINDS NIH HHS/ R01 GM054408/GM/NIGMS NIH HHS/ F31 NS064679-01A1/NS/NINDS NIH HHS/ R01GM54408/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural 2010/11/10 Genetics. 2011 Jan; 187(1):171-84. doi: 10.1534/genetics.110.123406. Epub 2010 Nov 8" |
