INPP5E Preserves Genomic Stability through Regulation of Mitosis

[en] The partially understood phosphoinositide signaling cascade regulates multiple aspects of cellular metabolism. Previous studies revealed that INPP5E, the inositol polyphosphate-5-phosphatase that is mutated in the developmental disorders Joubert and MORM syndromes, is essential for the function of the primary cilium and maintenance of phosphoinositide balance in nondividing cells. Here, we report that INPP5E further contributes to cellular homeostasis by regulating cell division. We found that silencing or genetic knockout of INPP5E in human and murine cells impairs the spindle assembly checkpoint, centrosome and spindle function, and maintenance of chromosomal integrity. Consistent with a cell cycle regulatory role, we found that INPP5E expression is cell cycle dependent, peaking at mitotic entry. INPP5E localizes to centrosomes, chromosomes, and kinetochores in early mitosis and shuttles to the midzone spindle at mitotic exit. Our findings identify the previously unknown, essential role of INPP5E in mitosis and prevention of aneuploidy, providing a new perspective on the function of this phosphoinositide phosphatase in health and development.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Sierra Potchanant, EA

Cerabona, D

Sater, ZA

He, Y

Sun, Z

Gehlhausen, J

Schurmans, Stéphane ; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > Biochimie métabolique vétérinaire

Gayral, S

Nalepa, G

Language :

English

Title :

INPP5E Preserves Genomic Stability through Regulation of Mitosis

Publication date :

2017

Journal title :

Molecular and Cellular Biology

ISSN :

0270-7306

eISSN :

1098-5549

Publisher :

American Society for Microbiology, Washington, United States - District of Columbia

Volume :

Issue :

Pages :

500-516

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 28 September 2017

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54 (4 by ULiège)

Number of downloads

69 (3 by ULiège)

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Bibliography

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