Local clustering of transferrin receptors promotes clathrin-coated pit initiation

Allen P. Liu, François Aguet, Gaudenz Danuser, Sandra L. Schmid

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

Clathrin-mediated endocytosis (CME) is the major pathway for concentrative uptake of receptors and receptor-ligand complexes (cargo). Although constitutively internalized cargos are known to accumulate into maturing clathrin-coated pits (CCPs), whether and how cargo recruitment affects the initiation and maturation of CCPs is not fully understood. Previous studies have addressed these issues by analyzing the global effects of receptor overexpression on CME or CCP dynamics. Here, we exploit a refined approach using expression of a biotinylated transferrin receptor (bTfnR) and controlling its local clustering using mono-or multivalent streptavidin. We show that local clustering of bTfnR increased CCP initiation. By tracking cargo loading in individual CCPs, we found that bTfnR clustering preceded clathrin assembly and confirmed that bTfnR-containing CCPs mature more efficiently than bTfnR-free CCPs. Although neither the clustering nor the related changes in cargo loading altered the rate of CCP maturation, bTfnR-containing CCPs exhibited significantly longer lifetimes than other CCPs within the same cell. Together these results demonstrate that cargo composition is a key source of the differential dynamics of CCPs.

Original languageEnglish (US)
Pages (from-to)1381-1393
Number of pages13
JournalJournal of Cell Biology
Volume191
Issue number7
DOIs
StatePublished - Dec 27 2010

ASJC Scopus subject areas

  • Cell Biology

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