CYTOSKELETON, PHOSPHOINOSITIDES AND SIGNAL TRANSDUCTION

Recent papers report interactions between cytoskeleton and phosphoinositide-cycle. These unexpected relationship between two different families of molecules seems to be very important for the control and the modulation of cytoskeleton organization as well as the regulation of signal transduction. Despite the difficulties to study in vivo the associations of proteins to lipids, the list of calcium and phosphoinositides regulated actin modulating protein is rapidly growing. One of the most interesting proteins from this list is the profilin. This protein binds to actin monomers as well as to phosphatidylinositol 4,5-bisphosphate (PIP2) and both compete for the same site on the profilin molecule. Since the affinity for PIP2 is higher, the complex profilin-actin can be dissociated by this phospholipid leading to actin polymerization. However, profilin is also able to control the phosphoinositide metabolism. When PIP2 binds to profilin, the unphosphorylated phospholipase C-gamma-1 is unable to hydrolyse PIP2. However, as soon as phospholipase C-gamma-1 is phosphorylated on specific tyrosine residues upon growth factor receptor activation, this protein becomes enzymatically active even if PIP2 binds to profilin, leading to the production of the second messengers inositol trisphosphate and diacylglycerol. A few other proteins similar to profilin, like gelsolin or vinculin, are discussed. On the other hand, it is of interest to note that evidence is accumulating that a population of some growth factor receptors is at least partly associated to the cytoskeleton. Also, a number of enzymes from the signal transduction cascade have in common homologous SH3 sequences. It is suggested that these types of sequences have a regulatory role in the association of proteins to cytoskeletal elements. An attractive hypothesis appears to be a coordinating function of the cytoskeleton. Indeed, cytoskeleton may provide the matrix to which various components of the signal transduction pathway are associated, thus enabling an efficient system for the regulation and the formation of the so-called signal transfer particles.