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First published online on April 5, 2007.
 Copyright © 2007 by The Physiological Society
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Received March 19, 2007
Revised March 22, 2007
Accepted after revision April 2, 2007

TARGET-SPECIFIC PIP2 SIGNALLING: HOW MIGHT IT WORK?

Nikita Gamper1* and Mark S Shapiro2

1 University of Leeds
2 University of Texas Health Science Center at San Antonio

* To whom correspondence should be addressed. E-mail: n.gamper{at}leeds.ac.uk.

Phosphatidylinositol 4,5-bisphosphate (PIP2)-mediated signalling is a new and rapidly developing area in the field of cellular signal transduction. With the extensive and growing list of PIP2-sensitive membrane proteins (many of which are ion channels and transporters) and multiple signals affecting plasma membrane PIP2 levels, the question arises as to the cellular mechanisms that confer specificity to PIP2-mediated signalling. In this review we critically consider two major hypotheses for such possible mechanisms: i) clustering of PIP2 in membrane microdomains with restricted lateral diffusion, a hypothesis providing mechanism for spatial segregation of PIP2 signals and ii) receptor-specific buffering of global plasma membrane PIP2 pool via Ca2+-mediated stimulation of PIP2 synthesis or release, a concept allowing for receptor-specific signalling with free lateral diffusion of PIP2. We also discuss several other technical and conceptual intricacies of PIP2-mediated signalling.


Key words: G-protein • Ion channel modulation • Phospholipid




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