Regulation of cyclin A localization downstream of Par-1 function is critical for the centrosome orientation checkpoint in Drosophila male germline stem cells.
Male germline stem cells (GSCs) in Drosophila melanogaster divide asymmetrically by orienting the mitotic spindle with respect to the niche, a microenvironment that specifies stem cell identity. The spindle orientation is prepared during interphase through stereotypical positioning of the centrosomes. We recently demonstrated that GSCs possess a checkpoint ("the centrosome orientation checkpoint") that monitors correct centrosome orientation prior to mitosis to ensure an oriented spindle and thus asymmetric outcome of the division. Here, we show that Par-1, a serine/threonine kinase that regulates polarity in many systems, is involved in this checkpoint. Par-1 shows a cell cycle-dependent localization to the spectrosome, a germline-specific, endoplasmic reticulum-like organelle. Furthermore, the localization of cyclin A, which is normally localized to the spectrosome, is perturbed in par-1 mutant GSCs. Interestingly, overexpression of mutant cyclin A that does not localize to the spectrosome and mutation in hts, a core component of the spectrosome, both lead to defects in the centrosome orientation checkpoint. We propose that the regulation of cyclin A localization via Par-1 function plays a critical role in the centrosome orientation checkpoint.
Life Sciences Institute, Center for Stem Cell Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA.
Hebao
H
Yuan
C-Y Ason
CY
Chiang
Jun
J
Cheng
Viktoria
V
Salzmann
Yukiko M
YM
Yamashita
D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D018385:Centrosome / Q000378:metabolism* / Q000502:physiology; D019925:Cyclin A / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology; D004331:Drosophila melanogaster / Q000196:embryology*; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3; D047468:Immunoprecipitation; D008297:Male; D008856:Microscopy, Fluorescence; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology; D008941:Spindle Apparatus / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D019925:Cyclin A; D029721:Drosophila Proteins; D017346:Protein Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; C472496:Par-1 protein, Drosophila