Disease relevance of RacGAP84C

• Since rotundRacGAP deletion leads to male sterility in the fruit fly, the mgcRacGAP gene may prove likewise to play a key role in mammalian male fertility [1].

Psychiatry related information on RacGAP84C

• Overexpression of RnRacGAP in pupae induces a number of phenotypes with distinct critical periods of induction [2].

High impact information on RacGAP84C

• The observed genetic interactions are consistent with a model in which Rac signaling is activated by Ras and negatively regulated by RnRacGAP during spermatid differentiation [3].
• RotundRacGAP functions with Ras during spermatogenesis and retinal differentiation in Drosophila melanogaster [3].
• These morphological phenotypes were rescued by genomic rnRacGAP transgenes, demonstrating that RnRacGAP function is critical to spermatid and retinal differentiation [3].
• In the male reproductive system, the absence of RnRacGAP induced small testes, empty seminal vesicles, short testicular cysts, reduced amounts of interspermatid membrane, the absence of individualization complexes, and incomplete mitochondrial condensation [3].
• In addition to being expressed in the imaginal discs, the m1.7 racGAP transcript was detected in developmentally specific germ line cells of the testes, the primary spermatocytes [4].

Biological context of RacGAP84C

• A Drosophila rotund transcript expressed during spermatogenesis and imaginal disc morphogenesis encodes a protein which is similar to human Rac GTPase-activating (racGAP) proteins [4].
• However, previous studies indicated that rotund racGAP was not responsible for the rotund phenotypes and that the rotund gene had yet to be identified [5].
• Alternative splicing of the Drosophila melanogaster rotundRacGAP gene [6].
• Unexpectedly, transgenes encoding Drac1N17, Dcdc42N17, or RotundRacGAP do not affect the c-Jun N-terminal kinase-dependent gene expression of decapentaplegic and puckered, indicating that another Drac1-independent signal redundantly activates this pathway [7].
• In cellularising embryos, ectopic RnRacGAP induces lethality, associated with radical cell-shape changes, apical F-actin delocalisation, and inhibition of basal actin polymerisation [2].

Anatomical context of RacGAP84C

• In situ hybridization experiments in human testis demonstrate a specific expression of mgcRacGAP mRNA in spermatocytes similar to that of rotundRacGAP in Drosophila testis [1].
• Furthermore, embryonic-directed expression of either RotundRacGAP, or dominant negative Drac1N17, transgenes induces similar defects in dorsal closure and inhibits Drac1-dependent cytoskeleton assembly at the leading edge [7].

Physical interactions of RacGAP84C

• Similarly, in yeast, RotundRacGAP interacts specifically with Drac1 and Dcdc42, as well as with their activated V12 forms, showing a particularly strong interaction with Dcdc42V12 [7].

Regulatory relationships of RacGAP84C

• To examine RnRacGAP function, we generated transgenic strains expressing RnRacGAP under the control of the heat-shock promoter hsp70 [2].

Other interactions of RacGAP84C

• The rotund (rn) gene in Drosophila melanogaster codes for a RacGTPase-activating protein, RnRacGAP [6].
• Here we demonstrate that Drosophila RotundRacGAP is active in vitro on Drac1 and Dcdc42 but not Drho1 [7].
• Thus, changes in cell shape/adhesion and reorganisation of the actin network are sensitive to overexpression of RnRacGAP throughout development in Drosophila [2].
• Only one RacGAP protein, RnRacGAP, has been identified in Drosophila [2].

References