RT Journal Article
SR Electronic
T1 Evidence of sinks and sources in the PLC activated PIP<sub>2</sub> cycle
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 183509
DO 10.1101/183509
A1 Rohit Suratekar
A1 Padinjat Raghu
A1 Sandeep Krishna
YR 2017
UL http://biorxiv.org/content/early/2017/09/01/183509.abstract
AB In many eukaryotic signalling cascades, receptor mediated phospholipase C (PLC) activity triggers phosphatidylinositol 4,5 bisphosphate (PIP2) hydrolysis leading to information transfer in cells. Coupled with PLC activation is a sequence of reactions spread across multiple compartments by which PIP2 is resynthesized, a process essential to maintain PIP2 levels and support sustained PLC signalling. The biochemical strategies to co-ordinate these reactions and support PIP2 levels have remained poorly understood. In particular, the question of whether the PIP2 cycle is a closed cycle with no net addition or loss of metabolites has not been addressed. Using mathematical modelling approaches, we find that a closed PIP2 cycle cannot explain experimentally observed changes in the metabolic intermediates when changing enzyme activities in the PIP2 cycle. Thus, we propose that the PIP2 cycle likely includes at least one metabolic source and one sink whose net activity results in the experimentally observed regulation of this key signalling pathway.