Abstract
Endocytosis of transmembrane receptors largely occurs via clathrin-coated vesicles that bud from the plasma membrane and deliver their cargo to the endosomal system for recycling or degradation. PIs (phosphoinositides) control the timing and localization of endocytic membrane trafficking by recruiting adaptors and other components of the transport machinery, thereby being part of a coincidence detection system in adaptor-mediated vesicle transport. Activation of organelle- and substrate-specific PI kinases by small GTPases such as Arf (ADP-ribosylation factor) and other factors may result in local changes of PI content, thereby regulating activity-dependent endocytic events including the recycling of synaptic vesicle membranes at nerve terminals. One such example is the PtdIns(4)P 5-kinase-mediated formation of PI(4,5)P2 [PtdIns(4,5)P2], which is required for the exo- and endo-cytic cycling of presynaptic vesicles and secretory granules. Over the last few years, protein X-ray crystallography in combination with biochemical and cell biological assays has been used to investigate the structure and function of many PI-binding proteins, including protein components of the endocytic machinery. These studies have provided molecular insights into the mechanisms by which PI(4,5)P2 recruits and activates adaptor proteins and their binding partners. In this mini-review, I will discuss the pathways of PI(4,5)P2 formation and its interactions with endocytic trafficking adaptors.
- adaptor
- ADP-ribosylation factor 6 (Arf6)
- clathrin
- endocytosis
- phosphoinositide
- trans-Golgi network
Footnotes
Cell Architecture: from Structure to Function: A Focus Topic at BioScience2005, held at SECC Glasgow, U.K., 17–21 July 2005. Edited by S. Cockroft (University College London, U.K.), Y. Goda (University College London, U.K.), R. Insall (Birmingham, U.K.) and M. Wakelam (Birmingham, U.K.).
Abbreviations: AP, adaptor protein complex; Arf, ADP-ribosylation factor; CALM, clathrin assembly lymphoid myeloid protein; CCP, clathrin-coated pit; CCV, clathrin-coated vesicle; PI, phosphoinositide; PI(4)P, PtdIns(4)P; PI(4,5)P2, PtdIns(4,5)P2; PIPK, PtdIns(4)P 5-kinase; SH, Src homology; TGN, trans-Golgi network
- © 2005 The Biochemical Society