UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

CHC22 and CHC17 clathrins have distinct biochemical properties and display differential regulation and function

Dannhauser, PN; Camus, SM; Sakamoto, K; Sadacca, LA; Torres, JA; Camus, MD; Briant, K; ... Brodsky, FM; + view all (2017) CHC22 and CHC17 clathrins have distinct biochemical properties and display differential regulation and function. Journal of Biological Chemistry , 292 (51) pp. 20834-20844. 10.1074/jbc.M117.816256. Green open access

[img]
Preview
Text
Brodsky_J. Biol. Chem.-2017-Dannhauser-20834-44.pdf - ["content_typename_Published version" not defined]

Download (3MB) | Preview

Abstract

Clathrins are cytoplasmic proteins that play essential roles in endocytosis and other membrane traffic pathways. Upon recruitment to intracellular membranes, the canonical clathrin triskelion assembles into a polyhedral protein coat that facilitates vesicle formation and captures cargo molecules for transport. The triskelion is formed by trimerization of three clathrin heavy-chain subunits. Most vertebrates have two isoforms of clathrin heavy chains, CHC17 and CHC22, generating two clathrins with distinct cellular functions. CHC17 forms vesicles at the plasma membrane for receptor-mediated endocytosis and at the trans-Golgi network for organelle biogenesis. CHC22 plays a key role in intracellular targeting of the insulin-regulated glucose transporter 4 (GLUT4), accumulates at the site of GLUT4 sequestration during insulin resistance, and has also been implicated in neuronal development. Here, we demonstrate that CHC22 and CHC17 share morphological features, in that CHC22 forms a triskelion and latticed vesicle coats. However, cellular CHC22-coated vesicles were distinct from those formed by CHC17. The CHC22 coat was more stable to pH change and was not removed by the enzyme complex that disassembles the CHC17 coat. Moreover, the two clathrins were differentially recruited to membranes by adaptors, and CHC22 did not support vesicle formation or transferrin endocytosis at the plasma membrane in the presence or absence of CHC17. Our findings provide biochemical evidence for separate regulation and distinct functional niches for CHC17 and CHC22 in human cells. Furthermore, the greater stability of the CHC22 coat relative to the CHC17 coat may be relevant to its excessive accumulation with GLUT4 during insulin resistance.

Type: Article
Title: CHC22 and CHC17 clathrins have distinct biochemical properties and display differential regulation and function
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1074/jbc.M117.816256
Publisher version: https://doi.org/10.1074/jbc.M117.816256
Language: English
Additional information: Copyright © 2017 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version free via Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0).
Keywords: CHC22 isoform, clathrin, coated vesicles, glucose metabolism, glucose transporter type 4 (GLUT4), insulin resistance, membrane trafficking, protein self-assembly, secretion, uncoating ATPase
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: http://discovery.ucl.ac.uk/id/eprint/10036036
Downloads since deposit
32Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item