Radmis, a novel mitotic spindle protein that functions in cell division of neural progenitors

Takahito Yumoto, Kazuhiko Nakadate, Yuki Nakamura, Yoshinobu Sugitani, Reiko Sugitani-Yoshida, Shuichi Ueda, Shin Ichi Sakakibara

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Developmental dynamics of neural stem/progenitor cells (NSPCs) are crucial for embryonic and adult neurogenesis, but its regulatory factors are not fully understood. By differential subtractive screening with NSPCs versus their differentiated progenies, we identified the radmis (radial fiber and mitotic spindle)/ckap2l gene, a novel microtubuleassociated protein (MAP) enriched in NSPCs. Radmis is a putative substrate for the E3-ubiquitin ligase, anaphase promoting complex/cyclosome (APC/C), and is degraded via the KEN box. Radmis was highly expressed in regions of active neurogenesis throughout life, and its distribution was dynamically regulated during NSPC division. In embryonic and perinatal brains, radmis localized to bipolar mitotic spindles and radial fibers (basal processes) of dividing NSPCs. As central nervous system development proceeded, radmis expression was lost in most brain regions, except for several neurogenic regions. In adult brain, radmis expression persisted in the mitotic spindles of both slowly-dividing stem cells and rapid amplifying progenitors. Overexpression of radmis in vitro induced hyperstabilization of microtubules, severe defects in mitotic spindle formation, and mitotic arrest. In vivo gain-of-function using in utero electroporation revealed that radmis directed a reduction in NSPC proliferation and a concomitant increase in cell cycle exit, causing a reduction in the Tbr2-positive basal progenitor population and shrinkage of the embryonic subventricular zone. Besides, radmis loss-of-function by shRNAs induced the multipolar mitotic spindle structure, accompanied with the catastrophe of chromosome segregation including the long chromosome bridge between two separating daughter nuclei. These findings uncover the indispensable role of radmis in mitotic spindle formation and cell-cycle progression of NSPCs.

Original languageEnglish
Article numbere79895
JournalPloS one
Volume8
Issue number11
DOIs
Publication statusPublished - 2013 Nov 8

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Yumoto, T., Nakadate, K., Nakamura, Y., Sugitani, Y., Sugitani-Yoshida, R., Ueda, S., & Sakakibara, S. I. (2013). Radmis, a novel mitotic spindle protein that functions in cell division of neural progenitors. PloS one, 8(11), [e79895]. https://doi.org/10.1371/journal.pone.0079895