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Dynamics and functions of phosphatidylinositol 3-phosphate binding proteins in cell division

Applicant Dr. Eva Wenzel
Subject Area Cell Biology
Term from 2011 to 2012
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 209380386
 
Phosphatidylinositol and its phosphorylated derivatives phosphatidylinositol-3-phosphate (PI(3)P) and phosphatidylinositol-3,5-bisphosphate PI(3,5)P2 are crucial regulators of diverse cellular functions such as signal transduction, autophagy and membrane trafficking. Their formation and turnover is tightly regulated by various kinases and phosphatases and disturbances in the phosphatidylinositol signalling have been implicated in autoimmune diseases, cardiovascular diseases and cancer (Pendaries et al, 2003). Recently a direct link between PI(3)P localized to the intercellular bridge and faulty genome separation was made (Sagona et al, 2010). Furthermore in a siRNA screen for PI(3)P-binding proteins involved in cell division several PI(3)P-binding proteins were identified, among them the kinase PIKfyve, which catalyses the formation of PI(3,5)P2 from PI(3)P. Knockdown of PIKfyve resulted in mitotic arrest and multinucleated cells (unpublished results). Here I propose to explore the turnover of PI(3)P in mitosis and cytokinesis and to study the dynamics and function of PI(3)P-binding proteins by focusing on PIKfyve. The following main questions will be addressed: What dynamics do PI(3)P and PI(3,5)P2 display during cell division in terms of abundance and localization? How are the PI(3)P and PI(3,5)P2 pools regulated? What is the role of PIKfyve during cell division? The required imaging equipment, diverse molecular biology methods and expertise in cell division analysis are available in the laboratory of Professor Stenmark.
DFG Programme Research Fellowships
International Connection Norway
 
 

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