The transmembrane adaptor protein, linker for activation of T cells (LAT), regulates RANKL-induced osteoclast differentiation

Mol Cells. 2012 Apr;33(4):401-6. doi: 10.1007/s10059-012-0009-2. Epub 2012 Feb 28.

Abstract

RANKL induces the formation of osteoclasts, which are responsible for bone resorption. Herein we investigate the role of the transmembrane adaptor proteins in RANKL-induced osteoclastogenesis. LAT positively regulates osteoclast differentiation and is up-regulated by RANKL via c-Fos and NFATc1, whereas LAB and LIME act as negative modulators of osteoclastogenesis. In addition, silencing of LAT by RNA interference or overexpression of a LAT dominant negative in bone marrow-derived macrophage cells attenuates RANKL-induced osteoclast formation. Furthermore, LAT is involved in RANKL-induced PLC(γ) activation and NFATc1 induction. Thus, our data suggest that LAT acts as a positive regulator of RANKL-induced osteoclastogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Bone Marrow Cells / cytology
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Gene Expression Regulation, Developmental*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism
  • Osteoclasts* / cytology
  • Osteoclasts* / metabolism
  • Phospholipase C gamma / genetics
  • Phospholipase C gamma / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Proto-Oncogene Proteins c-fos / deficiency
  • Proto-Oncogene Proteins c-fos / genetics
  • RANK Ligand / genetics
  • RANK Ligand / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Lat protein, mouse
  • Membrane Proteins
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • Phosphoproteins
  • Proto-Oncogene Proteins c-fos
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • Phospholipase C gamma