Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis

Marcel Mettlen, Dinah Loerke, Defne Yarar, Gaudenz Danuser, Sandra L. Schmid

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

Clathrin-mediated endocytosis of surface receptors and their bound ligands (i.e., cargo) is highly regulated, including by the cargo itself. One of the possible sources of the observed heterogeneous dynamics of clathrin-coated pits (CCPs) might be the different cargo content. Consistent with this, we show that CCP size and dynamic behavior varies with low density lipoprotein receptor (LDLR) expression levels in a manner dependent on the LDLR-specific adaptors, Dab2 and ARH. In Dab2-mCherry-expressing cells, varying LDLR expression leads to a progressive increase in CCP size and to the appearance of nonterminal endocytic events. In LDLR and ARH-mCherry-expressing cells in addition to an increase in CCP size, turnover of abortive CCPs increases, and the rate of CCP maturation decreases. Altogether, our results underscore the highly dynamic and cargo-responsive nature of CCP assembly and suggest that the observed heterogeneity is, in part, related to compositional differences (e.g., cargo and adaptors) between CCPs.

Original languageEnglish (US)
Pages (from-to)919-933
Number of pages15
JournalJournal of Cell Biology
Volume188
Issue number6
DOIs
StatePublished - Mar 22 2010

ASJC Scopus subject areas

  • Cell Biology

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