Regulation of endocytic clathrin dynamics by cargo ubiquitination

Henry, A. G., Hislop, J. N., Grove, J. , Thorn, K., Marsh, M. and von Zastrow, M. (2012) Regulation of endocytic clathrin dynamics by cargo ubiquitination. Developmental Cell, 23(3), pp. 519-532. (doi: 10.1016/j.devcel.2012.08.003) (PMID:22940114) (PMCID:PMC3470869)

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Some endocytic cargoes control clathrin-coated pit (CCP) maturation, but it is not known how such regulation is communicated. We found that μ-opioid neuropeptide receptors signal to their enclosing CCPs by ubiquitination. Nonubiquitinated receptors delay CCPs at an intermediate stage of maturation, after clathrin lattice assembly is complete but before membrane scission. Receptor ubiquitination relieves this inhibition, effectively triggering CCP scission and producing a receptor-containing endocytic vesicle. The ubiquitin modification that conveys this endocytosis-promoting signal is added to the receptor’s first cytoplasmic loop, catalyzed by the Smurf2 ubiquitin ligase, and coordinated with activation-dependent receptor phosphorylation and clustering through Smurf2 recruitment by the endocytic adaptor beta-arrestin. Epsin1 detects the signal at the CCP and is required for ubiquitin-promoted scission. This cargo-to-coat communication system mediates a biochemical checkpoint that ensures appropriate receptor ubiquitination for later trafficking, and it controls specific receptor loading into CCPs by sensing when a sufficient quorum is reached.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Grove, Dr Joe
Authors: Henry, A. G., Hislop, J. N., Grove, J., Thorn, K., Marsh, M., and von Zastrow, M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Developmental Cell
Publisher:Elsevier (Cell Press)
ISSN (Online):1878-1551
Published Online:30 August 2012
Copyright Holders:Copyright © 2012 Elsevier Inc.
First Published:First published in Developmental Cell 23(3): 519-532
Publisher Policy:Reproduced under a Creative Commons License

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