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Molecular and Cellular Biology, March 2003, p. 2162-2170, Vol. 23, No. 6
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.6.2162-2170.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Cortactin Is a Component of Clathrin-Coated Pits and Participates in Receptor-Mediated Endocytosis

Hong Cao,1 James D. Orth,1 Jing Chen,1 Shaun G. Weller,1 John E. Heuser,2 and Mark A. McNiven1*

Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905,1 Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 631302

Received 7 June 2002/ Returned for modification 3 July 2002/ Accepted 6 December 2002

The actin cytoskeleton is believed to contribute to the formation of clathrin-coated pits, although the specific components that connect actin filaments with the endocytic machinery are unclear. Cortactin is an F-actin-associated protein, localizes within membrane ruffles in cultured cells, and is a direct binding partner of the large GTPase dynamin. This direct interaction with a component of the endocytic machinery suggests that cortactin may participate in one or several endocytic processes. Therefore, the goal of this study was to test whether cortactin associates with clathrin-coated pits and participates in receptor-mediated endocytosis. Morphological experiments with either anti-cortactin antibodies or expressed red fluorescence protein-tagged cortactin revealed a striking colocalization of cortactin and clathrin puncta at the ventral plasma membrane. Consistent with these observations, cells microinjected with these antibodies exhibited a marked decrease in the uptake of labeled transferrin and low-density lipoprotein while internalization of the fluid marker dextran was unchanged. Cells expressing the cortactin Src homology three domain also exhibited markedly reduced endocytosis. These findings suggest that cortactin is an important component of the receptor-mediated endocytic machinery, where, together with actin and dynamin, it regulates the scission of clathrin pits from the plasma membrane. Thus, cortactin provides a direct link between the dynamic actin cytoskeleton and the membrane pinchase dynamin that supports vesicle formation during receptor-mediated endocytosis.

* Corresponding author. Mailing address: Dept. of Biochemistry and Molecular Biology, 1721 Guggenheim Building, Mayo Clinic, Rochester, MN 55905. Phone: (507) 284-0683. Fax: (507) 284-0762. E-mail: mcniven.mark{at}mayo.edu.

Molecular and Cellular Biology, March 2003, p. 2162-2170, Vol. 23, No. 6
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.6.2162-2170.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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