Cinderella story: PI4P goes from precursor to key signaling molecule

Abstract

Phosphatidylinositol lipids are signaling molecules involved in nearly all aspects of cellular regulation. Production of phosphatidylinositol 4-phosphate (PI4P) has long been recognized as one of the first steps in generating poly-phosphatidylinositol phosphates involved in actin organization, cell migration, and signal transduction. In addition, progress over the last decade has brought to light independent roles for PI4P in membrane trafficking and lipid homeostasis. Here, we describe recent advances that reveal the breadth of processes regulated by PI4P, the spectrum of PI4P effectors, and the mechanisms of spatiotemporal control that coordinate crosstalk between PI4P and cellular signaling pathways.

Novel Insights into the Role of the Smoothened Cysteine Rich Domain in Hedgehog Signalling

“…However, the observation that the synthetic PI(4)P moderately enhances SAG induced Hh signalling suggests that it might acts as a mimic of an allosteric activator of Smo. Furthermore, phosphatidylinositols are known to function as signalling molecules and regulate membrane trafficking of proteins [167,169]. Similarly PI(4)P may promote the membrane trafficking of Smo receptor and thereby render Smo active to induce downstream signalling.…”

“…Phosphatidylinositols are present in all cells and tissue types and are abundant in the brain tissues [167]. The phosphatidylinositols form a minor component of the membrane structures when compared to phosphatidylcholines and phosphatidylethanolamines [168].…”

“…The phosphatidylinositols form a minor component of the membrane structures when compared to phosphatidylcholines and phosphatidylethanolamines [168]. The inositol head group of the phosphatidylinositols are susceptible to phosphorylation at positions 3, 4 and 5 to produce seven different types of phosphatidylinositols [167,169]. The different phosphatidylinositols are functionally distinct and are enriched in different subcellular compartments.…”

“…Functionally, phosphatidylinositols and their derivatives play an important role in regulating cell migration, membrane trafficking and signal transduction [167,169]. The phosphatidylinositols have also been suggested to play a role in regulating Hh signalling by acting at the level of the Smo receptor [98,170].…”

“…The different phosphatidylinositols are functionally distinct and are enriched in different subcellular compartments. The specific lipid kinases and lipid phosphatases help in the inter-conversion of the phosphatidylinositols [167,169].…”