Disease relevance of RanGap

• The relevance of these findings to the mechanism leading to near sterility in homozygous SD males is discussed [1].

High impact information on RanGap

• Association between a satellite DNA sequence and the Responder of Segregation Distorter in D. melanogaster [2].
• It causes spermatids bearing it to degenerate after meiosis when the homologous second chromosome is a Segregation Distorter (SD) chromosome [3].
• That is, SD targets the Rsp locus on its homologue for destruction during spermatogenesis, causing meiotic drive [3].
• The Sd locus is the key distorting gene responsible for this phenotype [4].
• The only functional product encoded by this fragment is a truncated version of the RanGAP nuclear transport protein [4].

Biological context of RanGap

• Nuclear transport of a GFP reporter in salivary glands is impaired by SD, suggesting that a defect in nuclear transport may underlie sperm dysfunction [5].
• Here, we show that even wild-type RanGAP can cause segregation distortion when it is overexpressed in the male germ line or when the gene dosage of a particular modifier locus is increased [6].
• The severe eye phenotype caused by reduction of NTF2 is suppressed by loss of function mutations in chic and gain of function mutations in Sd (RanGAP) [7].
• The SD protein forms part of a transcriptional activation complex with the protein encoded by vestigial (vg) that, in turn, activates target genes important for wing formation [8].
• Segregation distorter chromosomes and the cryptic polymorphism form part of a coadapted complex which is associated with linkage disequilibrium in natrual populations [9].

Anatomical context of RanGap

• Our results suggest that there is strong up-regulation of one or several 2.0-2.3-kb transcripts from the duplicated region in the testes of an SD strain.(ABSTRACT TRUNCATED AT 250 WORDS)[10]
• The scheme, which is based on the meiotic drive system Segregation Distorter, results in the production of populations of zygotes that are almost exclusively of one sex [11].

Regulatory relationships of RanGap

• The key distorter locus, Sd, is a dominant neomorphic allele encoding a truncated, but enzymatically active, RanGAP (RanGTPase-activating protein) whose nuclear mislocalization underlies distortion by disrupting the Ran signaling pathway [6].
• The genetic structure of a segregation distorter chromosome (a derivative of SD-36) has been analyzed in a system in which recombination in the second chromosome is blocked by inversions except for the critical region around the centromeric heterochromatin [12].

Other interactions of RanGap

• We conclude that mislocalization of Sd-RanGAP causes distortion by reducing nuclear RanGTP, thereby disrupting the Ran signaling pathway [5].
• While the importance of this SD-binding domain has been clearly demonstrated both in vitro and in vivo, the remaining portions of VG have not been examined for in vivo function [13].

Analytical, diagnostic and therapeutic context of RanGap

• On northern blots, genomic probes from the tandem duplication detect an SD-specific 4-kb transcript in addition to several smaller transcripts present in both SD and SD+ [14].

References