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Elife. 2014 Oct 10;3. doi: 10.7554/eLife.04137.

A clathrin coat assembly role for the muniscin protein central linker revealed by TALEN-mediated gene editing.

Author information

1
Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States.
2
Department of Medicine, Washington University School of Medicine, St. Louis, United States.

Abstract

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.

KEYWORDS:

E. coli; TALEN; adaptor; biochemistry; cell biology; clathrin; endocytosis; human

PMID:
25303365
PMCID:
PMC4215538
DOI:
10.7554/eLife.04137
[Indexed for MEDLINE]
Free PMC Article

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