INTRODUCTION Clathrin coats function at the plasma membrane to promote rapid endocytosis of various receptors and other membrane proteins as well as soluble macromolecules and viruses

Clathrin coats function at the plasma membrane to promote rapid endocytosis of various receptors and other membrane proteins as well as soluble macromolecules and viruses (reviewed in Schmid, 1997). Clathrin-coated pits located in the trans-Golgi network (TGN) are essential for the receptormediated delivery of soluble enzymes to lysosomes (reviewed in Traub and Kornfeld, 1997). The major components of coated pits are the clathrin and the clathrin adaptor protein complexes or APs, AP-2 at the plasma membrane, and AP-1 in TGN (reviewed in Robinson, 1997). Each AP is a heterotetramer consisting of two 100-kDa subunits or adaptins (α/β2 in AP-2 and γ/β1 in AP-1), one 47/50-kDa (μ2 and μ1) and one 17/19kDa subunits (σ2 and σ1). Membrane-bound APs serve as nucleation sites for the assembly of the clathrin lattice. The clathrin-adaptor coats undergo rearrangements, resulting in invagination of the coated membrane and pinching off the coated vesicle. The plasma membrane and TGN-derived coated vesicles fuse with endosomes, which requires at least a partial dissociation of the clathrin lattice. Whether AP release from the membrane is a prerequisite for the vesicle fusion with the endosomal membrane is not known. However, restricted cellular localization of APs and other coat proteins suggests that the membrane docking and specific targeting of APs are tightly regulated. Current data suggest that α/γ, μ and possibly σ subunits of APs can be involved in the membrane-docking process (Gaidarov et al., 1996; Page and Robinson, 1995; Robinson, 1993). The anchoring molecules specific for AP-2 and AP-1 recruitment to the plasma membrane or TGN, respectively, are not identified. ADP-ribosylation factor, ARF1, is important for binding of AP-1 to TGN membranes (Traub et al., 1993). ARF requirement for AP-2 docking to plasma membrane has not been demonstrated (West et al., 1997). The latter study implicates phospholipase D-dependent production of phosphatidic acid in the recruitment of AP-2 at the plasma membrane. In addition, α-adaptins and possibly other subunits of AP-2 bind to phosphotidylinositols, which might be important for the membrane docking of AP-2 (Gaidarov et al., 317 Journal of Cell Science 112, 317-327 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 JCS0099