TY - JOUR
T1 - TTP specifically regulates the internalization of the transferrin receptor.
AU - Tosoni, Daniela
AU - Puri, Claudia
AU - Confalonieri, Stefano
AU - Salcini, Anna Elisabetta
AU - De Camilli, Pietro
AU - Tacchetti, Carlo
AU - Di Fiore, Pier Paolo
N1 - Keywords: Adaptor Proteins, Signal Transducing; Clathrin; Coated Pits, Cell-Membrane; Coated Vesicles; Dynamins; Endocytosis; Hela Cells; Humans; Models, Biological; Organelles; Protein Binding; RNA, Small Interfering; Receptors, Transferrin; Recombinant Fusion Proteins
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
U2 - 10.1016/j.cell.2005.10.021
DO - 10.1016/j.cell.2005.10.021
M3 - Journal article
C2 - 16325581
SN - 0092-8674
VL - 123
SP - 875
EP - 888
JO - Cell
JF - Cell
IS - 5
ER -