Clathrin light chains are required for the gyrating-clathrin recycling pathway and thereby promote cell migration

Nat Commun. 2014 May 23:5:3891. doi: 10.1038/ncomms4891.

Abstract

The clathrin light chain (CLC) subunits participate in several membrane traffic pathways involving both clathrin and actin, through binding the actin-organizing huntingtin-interacting proteins (Hip). However, CLCs are dispensable for clathrin-mediated endocytosis of many cargoes. Here we observe that CLC depletion affects cell migration through Hip binding and reduces surface expression of β1-integrin by interference with recycling following normal endocytosis of inactive β1-integrin. CLC depletion and expression of a modified CLC also inhibit the appearance of gyrating (G)-clathrin structures, known mediators of rapid recycling of transferrin receptor from endosomes. Expression of the modified CLC reduces β1-integrin and transferrin receptor recycling, as well as cell migration, implicating G-clathrin in these processes. Supporting a physiological role for CLC in migration, the CLCb isoform of CLC is upregulated in migratory human trophoblast cells during uterine invasion. Together, these studies establish CLCs as mediating clathrin-actin interactions needed for recycling by G-clathrin during migration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism
  • Animals
  • Cattle
  • Cell Movement*
  • Clathrin Heavy Chains / metabolism
  • Clathrin Light Chains / metabolism*
  • Endocytosis*
  • Female
  • Focal Adhesions / metabolism
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Integrin beta1 / metabolism
  • Models, Biological
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Transfection
  • Trophoblasts / cytology*
  • Trophoblasts / metabolism
  • Up-Regulation
  • Wound Healing

Substances

  • Actins
  • Clathrin Light Chains
  • Integrin beta1
  • RNA, Messenger
  • RNA, Small Interfering
  • Clathrin Heavy Chains