FAM29A, a target of Plk1 regulation, controls the partitioning of NEDD1 between the mitotic spindle and the centrosomes.
We previously showed that FAM29A, a spindle-associated protein, promotes microtubule-dependent microtubule amplification through its interaction with and recruitment of NEDD1, the targeting subunit of the gamma-tubulin ring complex. We report here that FAM29A is regulated by Plk1, a kinase essential for spindle assembly and its bipolarity. Plk1, FAM29A and NEDD1 form three separate complexes in vivo, not one single complex. Plk1 recruits FAM29A to spindle microtubules, which, in turn, targets NEDD1 to the spindle. Plk1 also recruits NEDD1 to the centrosomes, probably through a Plk1-NEDD1 interaction, but this interaction does not contribute to targeting NEDD1 to the spindle. Altering intracellular levels of FAM29A changes the distribution of NEDD1 between the centrosomes and the spindle, indicating that FAM29A controls the partition of NEDD1 between these two mitotic structures. Thus, Plk1 promotes microtubule nucleation from the centrosomes through a FAM29A-independent pathway and from the spindle through a FAM29A-dependent pathway. FAM29A controls the relative contributions of these two pathways to microtubule polymerization during mitosis.
Zhu
Hui
H
Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
Fang
Kayleen
K
Fang
Guowei
G
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D008941:Spindle Apparatus / Q000502:physiology*; D014162:Transfection; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1; C534027:HAUS6 protein, human; C509189:NEDD1 protein, human