Regulation of a LATS-homolog by Ras GTPases is important for the control of cell division

BMC Cell Biology

Gerald Weeks¹  Parvin Bolourani¹  Michael Schleicher²  Peter M Kastner²  Annette Müller-Taubenberger² 

[1] Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada;Anatomy III - Cell Biology, Ludwig Maximilian University of Munich, Schillerstr. 42, 80336 Munich, Germany

关键词: LATS kinase;    Ras GTPase;    Dictyostelium discoideum;    Cell division;   

Others  :  1088730
DOI  :  10.1186/1471-2121-15-25

 received in 2014-01-31, accepted in 2014-06-25,  发布年份 2014

【 摘 要 】

Background

Nuclear Dbf-related/large tumor suppressor (NDR/LATS) kinases have been shown recently to control pathways that regulate mitotic exit, cytokinesis, cell growth, morphological changes and apoptosis. LATS kinases are core components of the Hippo signaling cascade and important tumor suppressors controlling cell proliferation and organ size in flies and mammals, and homologs are also present in yeast and Dictyostelium discoideum. Ras proto-oncogens regulate many biological functions, including differentiation, proliferation and apoptosis. Dysfunctions of LATS kinases or Ras GTPases have been implicated in the development of a variety of cancers in humans.

Results

In this study we used the model organism Dictyostelium discoideum to analyze the functions of NdrC, a homolog of the mammalian LATS2 protein, and present a novel regulatory mechanism for this kinase. Deletion of the ndrC gene caused impaired cell division and loss of centrosome integrity. A yeast two-hybrid analysis, using activated Ras proteins as bait, revealed NdrC as an interactor and identified its Ras-binding domain. Further in vitro pull-down assays showed that NdrC binds RasG and RasB, and to a lesser extent RasC and Rap1. In cells lacking NdrC, the levels of activated RasB and RasG are up-regulated, suggesting a functional connection between RasB, RasG, and NdrC.

Conclusions

Dictyostelium discoideum NdrC is a LATS2-homologous kinase that is important for the regulation of cell division. NdrC contains a Ras-binding domain and interacts preferentially with RasB and RasG. Changed levels of both, RasB or RasG, have been shown previously to interfere with cell division. Since a defect in cell division is exhibited by NdrC-null cells, RasG-null cells, and cells overexpressing activated RasB, we propose a model for the regulation of cytokinesis by NdrC that involves the antagonistic control by RasB and RasG.

【 授权许可】

   
2014 Müller-Taubenberger et al.; licensee BioMed Central Ltd.

【 图 表 】

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