Clathrin Coats— Threads Laid Bare

vesicles, and possibly at other transport steps. Recent progress has provided insights into molecular interactions that govern clathrin coat dynamics. Now, ter Haar Babak Pishvaee and Gregory S. Payne Department of Biological Chemistry UCLA School of Medicine Los Angeles, California 90095 et al. (1998) report in this issue of Cell the crystal structure of the clathrin heavy chain amino-terminal domain, a site of key interactions within clathrin coats. Clathrin Coat Components Flux of membrane and proteins through secretory and endocytic pathways in eukaryotic cells is mediated by Two oligomeric protein complexes, clathrin and adaptor proteins (APs), are major constituents of clathrin coats transport vesicles. Genesis of these vesicles involves assembly of cytoplasmic coat protein complexes onto (reviewed in Schmid, 1997). Clathrin is a three-legged molecule, formed by C-terminal association of three the donor organelle membrane. Three basic classes of vesicle coats have been identified: clathrin, COPI, and elongated heavy chains (HC), each carrying a light chain (LC) (Figure 1B). The distinctive clathrin shape, a triskelCOPII (reviewed in Schmid, 1997, and references therein). Coats are thought to physically deform a patch of the ion, is well-adapted for assembly into polygonal arrays characteristic of clathrin coats (Figure 1C). In low ionic donor organelle membrane into a new vesicle and sequester selected membrane proteins into the emerging strength, mildly acidic, high Ca1 buffers, purified clathrin triskelia self-assemble into closed polyhedral cages revesicle (Figure 1A). Proteins packaged into coated vesicles include cargo in transit to other organelles and sembling the coats on transport vesicles. Removal of LC subunits from triskelia does not prevent cage formation, machinery to guide and dock each vesicle to the target organelle. Thus, coats have a central role in orchestratindicating that self-assembly is an inherent property of HC (Ungewickell and Ungewickell, 1991, and references ing traffic between membrane organelles. Once coated vesicles have formed, coat disassembly allows vesicle therein). However, compared to intact clathrin, LC-free triskelia assemble more readily in the absence of Ca1. fusion with the target membrane and returns coat complexes to the cytoplasm for additional cycles of vesicle These properties suggest that LC might inhibit spontaneous clathrin assembly, thereby ensuring assembly formation (Figure 1A). Since their discovery in the 1960s, clathrin coats have served as a paradigm for underonly at membrane sites destined for vesiculation (Ungewickell and Ungewickell, 1991). LC subunits can be standing the molecular basis of vesicle formation (reviewed in Schmid, 1997). Clathrin coats act at the plasma phosphorylated and bind Ca1, calmodulin, and hsc70, all potential regulatory components (Figure 1B). membrane to form endocytic transport vesicles, at the trans-Golgi network (TGN) to form endosome-targeted AP complexes act in both clathrin assembly and cargo