Dynamin, endocytosis and intracellular signalling

Dynamin is a neuronal phosphoprotein and a GTPase enzyme which mediates late stages of endocytosis in both neural and non-neural cells. Current knowledge about dynamin is reviewed with particular emphasis on its structure and regulation with respect to phosphorylation, protein-protein interactions and phospholipid binding. The major themes are the biochemical regulation of dynamin, its effects on dynamin's GTPase activity and how this might relate to assembling the 'fission ring' that brings about vesicle retrieval. Dynamin I is an isoform of the enzyme primarily located in the central and peripheral nervous systems, where it is enriched in areas of abundant synaptic contacts. Dynamin I undergoes protein-protein interactions via its proline-rich domain at the C-terminus and these can elevate its N-terminal GTPase activity. Dynamin I interacts with multiple proteins in the nerve terminal, including SH3 domain-containing proteins such as amphiphysin and potentially with other proteins such as beta gamma subunits. These regulate its role in endocytosis by targeting dynamin I to specific subcellular locations of retrieval. Dynamin I is phosphorylated in vivo by PKC and dephosphorylated on depolarization and calcium influx into nerve terminals in parallel with the coupled events of exocytosis and endocytosis. In late stages of synaptic vesicle retrieval dynamin I undergoes stimulated assembly into a collar, or fission ring, that surrounds the neck of recycling synaptic vesicles. Activation of GTP hydrolysis probably then generates the free synaptic vesicle, which can be refilled with neurotransmitters. This targeting and assembly may involve sequential steps including recruitment of AP-2 to synaptotagmin on the synaptic vesicle, and recruitment of amphiphysin, dynamin I, and synaptojanin. In addition to synaptic vesicle retrieval, dynamin has been associated with intracellular events mediated by growth factor receptors, insulin receptors and the beta-adrenergic receptor. This is likely to reflect targeting of these receptors for endocytosis soon after their activation. However, does it also suggest a broader role for dynamin in other aspects of intracellular signalling pathways?