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

doi:10.1016/j.cell.2005.10.021

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

80 Citations (Scopus)

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 language	English
Journal	Cell
Volume	123
Issue number	5
Pages (from-to)	875-88
Number of pages	13
ISSN	0092-8674
DOIs	https://doi.org/10.1016/j.cell.2005.10.021
Publication status	Published - 2005

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10.1016/j.cell.2005.10.021

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@article{27c94190519911dd8d9f000ea68e967b,

title = "TTP specifically regulates the internalization of the transferrin receptor.",

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.",

author = "Daniela Tosoni and Claudia Puri and Stefano Confalonieri and Salcini, {Anna Elisabetta} and {De Camilli}, Pietro and Carlo Tacchetti and {Di Fiore}, {Pier Paolo}",

note = "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",

year = "2005",

doi = "10.1016/j.cell.2005.10.021",

language = "English",

volume = "123",

pages = "875--88",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "5",

}

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 -

TTP specifically regulates the internalization of the transferrin receptor.

Abstract

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