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. (copyright)2005 Elsevier Inc.
|Titolo:||TTP specifically regulates the internalization of the transferrin receptor|
DI FIORE, PIER PAOLO (Ultimo)
|Parole Chiave:||article; endocytosis; internalization; morphology; priority journal; protein binding; protein expression; protein function; protein interaction; protein localization; protein phosphorylation; carrier proteins and binding proteins; clathrin; dynamin; protein subunit; transferrin receptor|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||dic-2005|
|Digital Object Identifier (DOI):||10.1016/j.cell.2005.10.021|
|Appare nelle tipologie:||01 - Articolo su periodico|