A Clathrin Coat Assembly Role for the Muniscin Protein Central Linker Revealed by TALEN-mediated Gene Editing
Authors
Affiliations
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.
Jin M, Iwamoto Y, Shirazinejad C, Drubin D Cell Rep. 2024; 43(12):114989.
PMID: 39580802 PMC: 11728081. DOI: 10.1016/j.celrep.2024.114989.
Sun Y, Yeam A, Kuo J, Iwamoto Y, Hu G, Drubin D PLoS Biol. 2024; 22(9):e3002833.
PMID: 39316607 PMC: 11451990. DOI: 10.1371/journal.pbio.3002833.
Jin M, Iwamoto Y, Shirazinejad C, Drubin D bioRxiv. 2024; .
PMID: 38712149 PMC: 11071352. DOI: 10.1101/2024.04.22.590579.
SGIP1 in axons prevents internalization of desensitized CB1R and modifies its function.
Durydivka O, Mackie K, Blahos J Front Neurosci. 2023; 17:1213094.
PMID: 37547151 PMC: 10397514. DOI: 10.3389/fnins.2023.1213094.
Lessons from the deep: mechanisms behind diversification of eukaryotic protein complexes.
Prokopchuk G, Butenko A, Dacks J, Speijer D, Field M, Lukes J Biol Rev Camb Philos Soc. 2023; 98(6):1910-1927.
PMID: 37336550 PMC: 10952624. DOI: 10.1111/brv.12988.