TY - JOUR TI - A clathrin coat assembly role for the muniscin protein central linker revealed by TALEN-mediated gene editing AU - Umasankar, Perunthottathu K AU - Ma, Li AU - Thieman, James R AU - Jha, Anupma AU - Doray, Balraj AU - Watkins, Simon C AU - Traub, Linton M A2 - Pfeffer, Suzanne R VL - 3 PY - 2014 DA - 2014/10/10 SP - e04137 C1 - eLife 2014;3:e04137 DO - 10.7554/eLife.04137 UR - https://doi.org/10.7554/eLife.04137 AB - Clathrin-mediated endocytosis is an evolutionarily ancient membrane transport system regulating cellular receptivity and responsiveness. Plasmalemma clathrin-coated structures range from unitary domed assemblies to expansive planar constructions with internal or flanking invaginated buds. Precisely how these morphologically-distinct coats are formed, and whether all are functionally equivalent for selective cargo internalization is still disputed. We have disrupted the genes encoding a set of early arriving clathrin-coat constituents, FCHO1 and FCHO2, in HeLa cells. Endocytic coats do not disappear in this genetic background; rather clustered planar lattices predominate and endocytosis slows, but does not cease. The central linker of FCHO proteins acts as an allosteric regulator of the prime endocytic adaptor, AP-2. By loading AP-2 onto the plasma membrane, FCHO proteins provide a parallel pathway for AP-2 activation and clathrin-coat fabrication. Further, the steady-state morphology of clathrin-coated structures appears to be a manifestation of the availability of the muniscin linker during lattice polymerization. KW - endocytosis KW - clathrin KW - TALEN KW - adaptor JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -