title: Regulation of dynein localization and centrosome positioning by Lis-1 and asunder during Drosophila spermatogenesis.
abstract: Dynein, a microtubule motor complex, plays crucial roles in cell-cycle progression in many systems. The LIS1 accessory protein directly binds dynein, although its precise role in regulating dynein remains unclear. Mutation of human LIS1 causes lissencephaly, a developmental brain disorder. To gain insight into the in vivo functions of LIS1, we characterized a male-sterile allele of the Drosophila homolog of human LIS1. We found that centrosomes do not properly detach from the cell cortex at the onset of meiosis in most Lis-1 spermatocytes; centrosomes that do break cortical associations fail to attach to the nucleus. In Lis-1 spermatids, we observed loss of attachments between the nucleus, basal body and mitochondria. The localization pattern of LIS-1 protein throughout Drosophila spermatogenesis mirrors that of dynein. We show that dynein recruitment to the nuclear surface and spindle poles is severely reduced in Lis-1 male germ cells. We propose that Lis-1 spermatogenesis phenotypes are due to loss of dynein regulation, as we observed similar phenotypes in flies null for Tctex-1, a dynein light chain. We have previously identified asunder (asun) as another regulator of dynein localization and centrosome positioning during Drosophila spermatogenesis. We now report that Lis-1 is a strong dominant enhancer of asun and that localization of LIS-1 in male germ cells is ASUN dependent. We found that Drosophila LIS-1 and ASUN colocalize and coimmunoprecipitate from transfected cells, suggesting that they function within a common complex. We present a model in which Lis-1 and asun cooperate to regulate dynein localization and centrosome positioning during Drosophila spermatogenesis.
authors: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, U-4225 Medical Research Building III, 465 21st Avenue South, Nashville, TN 37232-8240, USA.
authors: Poojitha
authors: P
authors: Sitaram
authors: Michael A
authors: MA
authors: Anderson
authors: Jeanne N
authors: JN
authors: Jodoin
authors: Ethan
authors: E
authors: Lee
authors: Laura A
authors: LA
authors: Lee
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D000072159:Dynactin Complex; D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D010641:Phenotype; D013087:Spermatids / Q000378:metabolism / Q000648:ultrastructure; D013090:Spermatocytes / Q000378:metabolism / Q000648:ultrastructure; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D000072159:Dynactin Complex; C513192:Lis-1 protein, Drosophila; D008869:Microtubule-Associated Proteins; C544294:asun protein, Drosophila; D004398:Dyneins