Cell Biology

Understanding Adaptors

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Science  19 Sep 2003:
Vol. 301, Issue 5640, pp. 1631
DOI: 10.1126/science.301.5640.1631c

Clathrin-coated pits mediate the internalization of clustered receptors from the cell surface in a process termed receptor-mediated endocytosis. Between the clathrin and the membrane-bound receptors is a layer of proteins known as adaptors. The AP-2 adaptor complex has been thought of as a key structural and functional component of plasma membrane-derived coated pits and vesicles, and it is found in stoichiometric amounts in isolated clathrin-coated vesicles. Now two groups, Motley et al. and Conner and Schmid, provide compelling evidence that challenges the assumption that AP-2 adaptors are necessary components of endocytic clathrin-coated vesicles. Motley et al. abrogated the expression of AP-2 in tissue culture cells using RNA interference. Clathrin-coated pits at the plasma membrane were reduced 12-fold; however, only receptor-mediated endocytosis of the transferrin receptor was severely compromised. Epidermal growth factor receptor-mediated uptake and low-density lipoprotein receptor-mediated uptake were unaffected. Conner and Schmid overexpressed an accessory kinase that inhibits AP-2 function and similarly found selective effects on the uptake of different receptors from the cell surface. Thus AP-2 is not essential for clathrin-coated vesicle formation at the plasma membrane, and AP-2 can be viewed simply as one adaptor among many involved in the recruitment of different receptors to clathrin-coated pits. — SMH

J. Cell Biol. 162, 909; 773 (2003).

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