Central regulation of locomotor behavior of Drosophila melanogaster depends on a CASK isoform containing CaMK-like and L27 domains.
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-β), but do not affect transcripts encoding the smaller forms (CASK-α), 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-β mutant, however, cannot be rescued by expression of a CASK-β 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-β, while widely expressed in the nervous system, appears to have a unique role within central circuits that control motor output.
Department of Biology, Volen Center for Complex Systems and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts 02454-9110, USA.
Justin B
JB
Slawson
Elena A
EA
Kuklin
Aki
A
Ejima
Konark
K
Mukherjee
Lilly
L
Ostrovsky
Leslie C
LC
Griffith
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002874:Chromosome Mapping; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics; D003380:Courtship; D004331:Drosophila melanogaster / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D056426:Genetic Loci / Q000235:genetics; D051528:Guanylate Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006185:Habituation, Psychophysiologic / Q000187:drug effects / Q000235:genetics; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000235:genetics; D016296:Mutagenesis; D010675:Pheromones / Q000494:pharmacology; D011494:Protein Kinases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion
D007527:Isoenzymes; D010675:Pheromones; D012333:RNA, Messenger; D011494:Protein Kinases; C106868:CASK kinases; D051528:Guanylate Kinases