title: Closing the (Ran)GAP on segregation distortion in Drosophila.
abstract: Segregation Distorter (SD) is a meiotic drive system in Drosophila that causes preferential transmission of the SD chromosome from SD/SD(+) males owing to induced dysfunction of SD(+) spermatids. Since its discovery in 1956, SD and its mode of action have baffled biologists. Recently, substantial progress has been made in elucidating this puzzle. Sd, the primary gene responsible for distortion encodes a mutant RanGAP, a key protein in the Ran signaling pathway required for nuclear transport and other nuclear functions. The mutant protein is enzymatically active but mislocalized to nuclei, which apparently disrupts Ran signaling by reducing intranuclear Ran-GTP levels. Some evidence suggests that a defect in nuclear transport may be the main cause of sperm dysfunction. Although important questions remain, the basic mechanism of distortion is now understood sufficiently well that specific hypotheses can be formulated and tested. This previously mysterious genetic system may now offer unique insights into novel aspects of regulation by Ran.
authors.affiliation: Laboratory of Genetics, University of Wisconsin, Madison 53706, USA.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kusano
authors.forename: Cynthia
authors.initials: C
authors.lastname: Staber
authors.forename: Ho Yin Edwin
authors.initials: HY
authors.lastname: Chan
authors.forename: Barry
authors.initials: B
authors.lastname: Ganetzky
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D017344:Genes, Insect; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D013094:Spermatozoa / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; C118002:RanGAP protein, Drosophila