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Evolution and function of a novel clathrin isoform
Author(s) -
Brodsky Frances M.,
Esk Christopher,
Hoshino Sachiko,
Vassilopoulos Stéphane
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.319.1
Subject(s) - clathrin , microbiology and biotechnology , endosome , biology , glut4 , endocytosis , golgi apparatus , organelle biogenesis , signal transducing adaptor protein , intracellular , receptor , biogenesis , glucose transporter , signal transduction , gene , biochemistry , endoplasmic reticulum , insulin , endocrinology
Clathrin forms a lattice‐like intracellular membrane coat to organize adaptor molecules that interact with transmembrane protein cargo. This process facilitates protein sorting at the plasma membrane, on endosomes and in the trans‐Golgi network (TGN). The CHC17 isoform of the clathrin heavy chain is ubiquitously expressed in vertebrate tissues and plays a key role in receptor‐mediated endocytosis and lysosome biogenesis. A CHC17 ortholog is present in all eukaryotes where it performs related functions. During vertebrate evolution, a second isoform of clathrin heavy chain CHC22 arose by gene duplication. CHC22 is expressed highly in human skeletal muscle and adipocytes and at lower levels in other human cell types. CHC22 function is restricted primarily to the endosome‐TGN region of the cell, where it influences retrograde transport from endosomes to the TGN. In muscle cells and adipocytes, CHC22 regulates the formation of the storage compartment from which the GLUT4 glucose transporter is released upon insulin stimulation. The CHC22 gene was found to be a pseudogene in mice, revealing species‐restricted differences in membrane traffic components involved in glucose homeostasis. CHC22 appears to function by competition with CHC17 for clathrin adaptors. When introduced as a transgene into mice, it alters membrane traffic pathways involved in GLUT4 function and induces diabetic symptoms. Consistent with this observation, CHC22 distribution is altered in human patients with type 2 diabetes. This novel and species‐restricted function of CHC22 clathrin contributes to evolutionary diversity of metabolic pathways that have relevance to understanding human diabetes.