HGAL localization to cell membrane regulates B-cell receptor signaling

Xiaoqing Lu, Renaud Sicard, Xiaoyu Jiang, Jessica N. Stockus, George McNamara, Midhat Abdulreda, Vincent T. Moy, Ralf Landgraf, Izidore S. Lossos

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Human germinal center-associated lymphoma (HGAL) is specifically expressed only in germinal center (GC) B lymphocytes and GC-derived lymphomas. HGAL protein decreases lymphocyte motility by inhibiting the ability of myosin to translocate actin via direct interaction with F-actin and myosin II and by activating RhoA signaling via direct interactions with RhoA-specific guanine nucleotide exchange factors. HGAL protein also regulates B-cell receptor (BCR) signaling by directly binding to and enhancing Syk kinase activity and activation of its downstream effectors. Herein we demonstrate that HGAL protein can be myristoylated and palmitoylated and that these modifications localize HGAL to cellular membrane raft microdomains with distinct consequences for BCR signaling and chemoattractant-induced cell mobility. In BCR signaling, raft localization of HGAL facilitates interaction with Syk and modulation of the BCR activation and signaling, which induces HGAL phosphorylation and redistribution fromlipid raft to bulkmembrane and cytoplasm, followed by degradation. In contrast, HGAL myristoylation and palmitoylation avert its inhibitory effects on chemoattractant-induced cell motility. These findings further elucidate the growing and complex role of HGAL in B-cell biology and suggest that membrane-bound and cytoplasmic HGAL protein differently regulates distinct biological processes.

Original languageEnglish (US)
Pages (from-to)649-657
Number of pages9
JournalBlood
Volume125
Issue number4
DOIs
StatePublished - Jan 22 2015

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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