Nuclear mislocalization of enzymatically active RanGAP causes segregation distortion in Drosophila

Dev Cell. 2001 Sep;1(3):351-61. doi: 10.1016/s1534-5807(01)00042-9.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Cell Nucleus / metabolism*
  • Chromosome Segregation*
  • Drosophila Proteins*
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Female
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Genes, Reporter
  • Immunohistochemistry
  • Insect Proteins / genetics
  • Insect Proteins / metabolism
  • Male
  • Meiosis / physiology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Salivary Glands / cytology
  • Salivary Glands / physiology
  • Spermatocytes / metabolism
  • Testis / metabolism
  • Transgenes


  • Drosophila Proteins
  • GTPase-Activating Proteins
  • Insect Proteins
  • RanGAP protein, Drosophila
  • Recombinant Fusion Proteins