GRAIL (gene related to anergy in lymphocytes) regulates cytoskeletal reorganization through ubiquitination and degradation of Arp2/3 subunit 5 and coronin 1A

Daiju Ichikawa, Miho Mizuno, Takashi Yamamura, Sachiko Miyake

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Anergy is an important mechanism for the maintenance of peripheral tolerance and avoidance of autoimmunity. The upregulation of E3 ubiqitin ligases, including GRAIL (gene related to anergy in lymphocytes), is a key event in the induction and preservation of anergy in T cells. However, the mechanisms of GRAIL-mediated anergy induction are still not completely understood. We examined which proteins serve as substrates for GRAIL in anergic T cells. Arp2/3-5 (actin-related protein 2/3 subunit 5) and coronin 1A were polyubiquitinated by GRAIL via Lys-48 and Lys-63 linkages. In anergic T cells and GRAIL-overexpressed T cells, the expression of Arp2/3-5 and coronin 1A was reduced. Furthermore, we demonstrated that GRAIL impaired lamellipodium formation and reduced the accumulation of F-actin at the immunological synapse. GRAIL functions via the ubiquitination and degradation of actin cytoskeleton-associated proteins, in particular Arp2/3-5 and coronin 1A. These data reveal that GRAIL regulates proteins involved in the actin cytoskeletal organization, thereby maintaining the unresponsive state of anergic T cells.

Original languageEnglish
Pages (from-to)43465-43474
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number50
DOIs
Publication statusPublished - 2011 Dec 16

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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