BBB seminar 29.03.2012

Cell function is dependent upon the coordinated and dynamic formation of biomolecular interaction networks between molecules of diverse biochemical properties. While protein-protein interactions have been a major focus, proteins are also regulated by important signalling lipid molecules, namely the phosphorylated derivatives of phosphatidylinositol (PtdIns), collectively known as phosphoinositides (PIs). PIs are implicated in the control of a myriad of cellular functions, particularly in the cytoplasm, where they are perceived as spatial organisers of proteins. Over the past 20 years, it has become clear that a nuclear PI cycle also exists, which is regulated independently of the cytosolic PI pathway. PIs have been implicated in nuclear processes such as transcription, pre-mRNA splicing/processing as well as proliferation and cell cycle regulation. However, the precise mechanisms by which PIs regulate these processes are largely unknown.

Our lab focuses on protein-PI interaction networks and we analyse their composition, regulation as well as their functional roles in the cell nucleus. In addition, our goal is to understand how these networks are remodelled in healthy and pathological states where the PI metabolic pathways are known to be altered (particularly in obesity, type 2 diabetes mellitus, cancer). I will present published [1, 2] as well as new data on the identification of phosphatidylinositol 4,5 bisphosphate (PtdIns(4,5)P₂) effector proteins as well as their potential roles in the nucleus.

References:

1. Lewis, A.E., et al. Identification of nuclear phosphatidylinositol 4,5-bisphosphate-interacting proteins by neomycin extraction. Mol Cell Proteomics, 2011. 10(2): M110 003376.

2. D'Santos, C.S. and Lewis, A.E. Functional Proteomics: Mapping Lipid-Protein Interactomes. Integrative Proteomics, 2012. Hon-Chiu Eastwood Leung (Ed.), ISBN: 978-953-51-0070-6, InTech. Available from: http://www.intechopen.com/articles/show/title/functional-proteomics-mapp...