|  Help  |  About  |  Contact Us

Publication : ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules.

First Author  Gai M Year  2016
Journal  EMBO Rep Volume  17
Issue  10 Pages  1396-1409
PubMed ID  27562601 Mgi Jnum  J:236076
Mgi Id  MGI:5804697 Doi  10.15252/embr.201541823
Citation  Gai M, et al. (2016) ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules. EMBO Rep 17(10):1396-1409
abstractText  Correct orientation of cell division is considered an important factor for the achievement of normal brain size, as mutations in genes that affect this process are among the leading causes of microcephaly. Abnormal spindle orientation is associated with reduction of the neuronal progenitor symmetric divisions, premature cell cycle exit, and reduced neurogenesis. This mechanism has been involved in microcephaly resulting from mutation of ASPM, the most frequently affected gene in autosomal recessive human primary microcephaly (MCPH), but it is presently unknown how ASPM regulates spindle orientation. In this report, we show that ASPM may control spindle positioning by interacting with citron kinase (CITK), a protein whose loss is also responsible for severe microcephaly in mammals. We show that the absence of CITK leads to abnormal spindle orientation in mammals and insects. In mouse cortical development, this phenotype correlates with increased production of basal progenitors. ASPM is required to recruit CITK at the spindle, and CITK overexpression rescues ASPM phenotype. ASPM and CITK affect the organization of astral microtubules (MT), and low doses of MT-stabilizing drug revert the spindle orientation phenotype produced by their knockdown. Finally, CITK regulates both astral-MT nucleation and stability. Our results provide a functional link between two established microcephaly proteins.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

12 Bio Entities

Trail: Publication

11 Expression

Trail: Publication