WNK1 is required for mitosis and abscission

Szu-wei Tu et al., PNAS 10:1073 (2010)

Speaker: Wang Yu-Ren (王昱仁)                                          Time: 15:10-16:00, Feb. 23, 2011

Commentator: Dr. Wang Shu-Ying (王淑鶯 老師)             Place: Room 601

Abstract

WNK (with no K) protein kinase was first cloned in 2000 and so named because there is no lysine (K) in its catalytic domain when comparing with the typical protein kinase. So far, there are four members had been found in the WNK family and each has inhibitory function to others. The WNK1 had been proved associated with familial hyperkalemic hypertension (FHH) and several cancers (1). The WNK1, there are evidences suggest that WNK1 can promote cell proliferation through the MAPK pathway (2). According to these, the authors intended to study what role does WNK1 plays in the cell cycle by cell-based screens. First, they used transient antibody staining with endogenous WNK1 and observed that displayed a punctate cytoplasmic pattern. Interesting, when they knocked down the WNK1 to confirm the staining, there were some cells had division defect. To understand this phenomenon, they stained the endogenous WNK1 and found that WNK1 was concentrated on mitotic spindle during mitosis. However, when down regulated WNK1 by siRNA cause unusual mitotic spindle and chromosome alignment even reduced survival rate due to cytokinesisfail. As the results of the same group’s discovery (3) and several published suggest that OSR1 would be phosphorylated by WNK1, so the authors used siRNA again to identify this association. Surprisingly, knocked down OSR1 does not have the same effect as the siWNK1. In addition, other WNKs expression except for WNK1 was unable to be detect by immunoblotting in the using cell line. According to these finding, the authors suggest that WNK1 not only involve in hypertension and cancer but also has a crucial role to irrelevant to other WNKs and OSR1 by together with microtubules in mammalian cell mitosis and cytokinesis.

References

1.          JAMES A. McCORMICK et al., The WNKs: Atypical Protein Kinases With Pleiotropic Actions. Physiol Rev 91: 177-219 (2011).

2.          So’nia Moniz et al., Emerging roles for WNK kinases in cancer. Cell. Mol. Life Sci. 67:1265-76 (2010)

3.          Melanie H. Cobb et al., WNK1 and OSR1 regulate the Na⁺, K⁺, 2Cl^- cotransporter in HeLa cells. PNAS 29:10883-10888 (2006)