THE AMPHIPHYSIN FAMILY OF PROTEINS AND THEIR ROLE IN ENDOCYTOSIS AT THE SYNAPSE

Clathrin-mediated endocytosis at the plasma membrane is a major pathwa y of synaptic vesicle recycling in neurones, but little is known about the molecular machinery that orchestrates the process.The amphiphysin protein has recently emerged into the limelight since its discovery i n 1992 as a synaptic vesicle-associated protein. It was subsequently f ound to interact in vitro with the GTPase dynamin through its SH3 doma in. However, only in the past year has its role in endocytosis been co nfirmed, with the demonstration that the introduction of dominant-nega tive-acting SH3 domains into living cells causes a potent blockade of clathrin-mediated endocytosis.This, together with the discovery by sev eral groups of a second nerve terminal-enriched amphiphysin isoform, a nd the finding that the two proteins heterodimerize, further suggests that the amphiphysins are closely connected with dynamin-mediated vesi cle budding,This review summarizes current views in the field, and dra ws on data that suggest intriguing alternative roles - including possi ble involvement in the cytoskeleton and in tumour suppression - for ce rtain members of the amphiphysin family.