The TRP superfamily of cation channels encompasses 28 mammalian members related to the product of the Drosophila trp (transient receptor potential) gene. TRP channels have a widespread distribution in many cell types and organs and gate in response to a broad variety of physical and chemical stimuli; as such, they can be considered as ubiquitous cellular sensors. Several recent studies reported modulation of different TRP channels by phosphoinositides, in particular by phosphatidylinositol 4,5-bisphosphate (PIP2). In most cases, PIP2 promotes TRP channel activation. Here we provide a brief overview of current insights and controversies about the mechanisms and structural determinants of PIP2–TRP channel interactions, and zoom in on the regulation of the Ca2+- and voltage-gated TRPM4 by phosphoinositides.
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