title: Nuclear mislocalization of enzymatically active RanGAP causes 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 dysfunction of SD+ spermatids. The Sd locus, which is essential for distortion, encodes a truncated RanGAP (Ran GTPase activating protein), a key nuclear transport factor. Here, we show that Sd-RanGAP retains normal enzyme activity but is mislocalized to nuclei. Distortion is abolished when enzymatic activity or nuclear localization of Sd-RanGAP is perturbed. Overexpression of Ran or RanGEF (Ran GTPase exchange factor) in the male germline fully suppresses distortion. We conclude that mislocalization of Sd-RanGAP causes distortion by reducing nuclear RanGTP, thereby disrupting the Ran signaling pathway. Nuclear transport of a GFP reporter in salivary glands is impaired by SD, suggesting that a defect in nuclear transport may underlie sperm dysfunction.
authors.affiliation: Laboratory of Genetics, University of Wisconsin-Madison, 53706, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kusano
authors.forename: C
authors.initials: C
authors.lastname: Staber
authors.forename: B
authors.initials: B
authors.lastname: Ganetzky
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D020090:Chromosome Segregation; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D007150:Immunohistochemistry; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000166:cytology / Q000502:physiology; D013090:Spermatocytes / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D019076:Transgenes
chemical_list: D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; D019476:Insect Proteins; C118002:RanGAP protein, Drosophila; D011993:Recombinant Fusion Proteins