Fig. 7. Model for the regulation of profilin-I-actin interaction by PtdIns(4,5)P₂ during neurite formation and growth. NGF stimulation locally activates PLC1, causing PtdIns(4,5)P₂ hydrolysis into inositol 3-phosphate (IP₃) and diacylglycerol (DAG), and release of profilin I (and perhaps also profilin IIa), that can now interact with actin and stimulate neurite formation. In this early stage, RhoA is inactivated through Rac and phosphoinositide 3-kinase (PI3K). At later stages, RhoA becomes active again, thereby activating ROCK and forming a complex with profilin IIa, which is now inactivated. ROCK also activates PtdIns 5-kinase (PI5K), which again increases the local PtdIns(4,5)P₂ levels, resulting in inactivation of profilin I. Continuous stimulation of the NGF-receptor starts the PtdIns(4,5)P₂ hydrolysis cycle again, and creates a balanced level of free profilin I, which may then contribute to neurite elongation. Where inactive, proteins are shown in grey lettering.