WNK1 is required for mitosis and abscission

Szu Wei Tu, Abhijit Bugde, Katherine Luby-Phelps, Melanie H. Cobb

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

WNK [with no lysine (K)] protein kinases are found in all sequenced multicellular and many unicellular organisms. WNKs influence ion balance. Two WNK family members are associated with a single gene form of hypertension. RNA interference screens have implicatedWNKs in survival and growth, andWNK1 is essential for viability of mice.We found that the majority of WNK1 is localized on cytoplasmic puncta in resting cells. During cell division, WNK1 localizes to mitotic spindles. Therefore, we analyzed mitotic phenotypes in WNK1 knockdown cells. A large percentage of WNK1 knockdown cells fail to complete cell division, displaying defects in mitotic spindles and also in abscission and cell survival. One of the best characterized WNK1 targets is the protein kinase OSR1 (oxidative stress responsive 1). OSR1 regulates ion cotransporters, is activated in response to osmotic stress by WNK family members, and is largely associated with WNK1. In resting cells, the majority of OSR1, like WNK1, is on cytoplasmic puncta. OSR1 is also in nuclei. In contrast to WNK1, however, OSR1 does not concentrate around spindles during mitosis and does not show a WNK1-like localization pattern in mitotic cells. Knockdown of OSR1 has only a modest effect on cell survival and does not lead to spindle defects. We conclude that decreased cell survival associated with loss of WNK1 is attributable to defects in chromosome segregation and abscission and is independent of the effector kinase OSR1.

Original languageEnglish (US)
Pages (from-to)1385-1390
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number4
DOIs
StatePublished - Jan 25 2011

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Mitosis
Oxidative Stress
Cell Survival
Spindle Apparatus
Cell Division
Protein Kinases
Ions
Osmoregulation
Chromosome Segregation
RNA Interference
Lysine
Phosphotransferases
Hypertension
Phenotype
Growth
Genes

Keywords

  • Alanine-rich kinase
  • Cytokinesis
  • Microtubules
  • Proline-
  • Serine-

ASJC Scopus subject areas

  • General

Cite this

WNK1 is required for mitosis and abscission. / Tu, Szu Wei; Bugde, Abhijit; Luby-Phelps, Katherine; Cobb, Melanie H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 4, 25.01.2011, p. 1385-1390.

Research output: Contribution to journalArticle

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