ASPM and citron kinase co-localize to the midbody ring during cytokinesis.
Mutations in ASPM (abnormal spindle-like microcephaly associated) and citron kinase (CITK) cause primary microcephaly in humans and rodents, respectively. Both proteins are expressed during neurogenesis and play important roles in neuronal progenitor cell division. ASPM is localized to the spindle pole, and is essential for maintaining proliferative cell division. CITK is present at the cytokinesis furrow and midbody ring, and it is essential for cellular abscission. We report here that ASPM also localizes to the midbody ring in mammalian cells. ASPM co-localizes with CITK at the midbody ring and coimmunoprecipitates with CITK in lysates prepared from HeLa cells and embryonic neuroepithelium. Furthermore, a GFP-tagged fragment of the N-terminus of ASPM localizes to centrosomes and spindle poles, while a GFP-tagged fragment of the C-terminus localizes to midbodies. All reported ASPM mutations that cause microcephaly involve a truncation or mutation of the C-terminus. In addition, at least two other microcephaly-related proteins, CENPJ and CDK5RAP2, previously localized to spindle poles, also localize to midbodies. Together our observations support a model of neurogenesis in which spindle dynamics and cellular abscission are coordinated.
Paramasivam
Murugan
M
Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269, USA.
Chang
Yoon Jeung
YJ
LoTurco
Joseph J
JJ
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D048749:Cytokinesis; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019579:Neocortex / Q000196:embryology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D008941:Spindle Apparatus / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism
C467202:ASPM protein, human; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C115635:citron-kinase; D017346:Protein Serine-Threonine Kinases