FYVE finger proteins as effectors of phosphatidylinositol 3-phosphate

Phosphatidylinositol 3-phosphate (PtdIns(3)P), generated via the phosphoryl ation of phosphatidylinositol by phosphatidylinositol 3-kinase (PI 3-kinase ), plays an essential role in intracellular membrane traffic. The underlyin g mechanism is still not understood in detail, but the recent identificatio n of the FYVE finger as a protein domain that binds specifically to PtdIns( 3)P provides a number of potential effecters for PtdIns(3)P. The FYVE finge r (named after the first letter of the four proteins containing it; Fablp, YOTB, Vaclp and EEAl) is a double-zinc binding domain that is conserved in more than 30 proteins from yeast to mammals. It is found in several protein s involved in intracellular traffic, and FYVE finger mutations that affect zinc binding are associated with the loss of function of several of these p roteins. The interaction of FYVE fingers with PtdIns(3)P may serve three al ternative functions: First, to recruit cytosolic FYVE finger proteins to Pt dIns(3)P-containing membranes (in concert with accessory molecules); second , to enrich for membrane bound FYVE finger proteins into PtdIns(3)P contain ing microdomains within the membrane; and third, to modulate the activity o f membrane bound FYVE finger proteins. (C) 1999 Elsevier Science Ireland Lt d. All rights reserved.