TTP specifically regulates the internalization of the transferrin receptor

Daniela Tosoni, Claudia Puri, Stefano Confalonieri, Anna Elisabetta Salcini, Pietro De Camilli, Carlo Tacchetti, Pier Paolo Di Fiore

Research output: Contribution to journalArticle

Abstract

Different plasma membrane receptors are internalized through saturable/noncompetitive pathways, suggesting cargo-specific regulation. Here, we report that TTP (SH3BP4), a SH3-containing protein, specifically regulates the internalization of the transferrin receptor (TfR). TTP interacts with endocytic proteins, including clathrin, dynamin, and the TfR, and localizes selectively to TfR-containing coated-pits (CCP) and -vesicles (CCV). Overexpression of TTP specifically inhibits TfR internalization, and causes the formation of morphologically aberrant CCP, which are probably fission impaired. This effect is mediated by the SH3 of TTP, which can bind to dynamin, and it is rescued by overexpression of dynamin. Functional ablation of TTP causes a reduction in TfR internalization, and reduced cargo loading and size of TfR-CCV. Tyrosine phosphorylation of either TTP or dynamin prevents their interaction, pointing to a possible mechanism of exclusion of TTP from some CCP. Thus, TTP might represent one of the long sought for molecules that allow cargo-specific control of clathrin endocytosis.

Original languageEnglish
Pages (from-to)875-888
Number of pages14
JournalCell
Volume123
Issue number5
DOIs
Publication statusPublished - Dec 2 2005

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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