Pular para o conteúdo
Merck

Cell surface-bound La protein regulates the cell fusion stage of osteoclastogenesis.

Nature communications (2023-02-05)
Jarred M Whitlock, Evgenia Leikina, Kamran Melikov, Luis Fernandez De Castro, Sandy Mattijssen, Richard J Maraia, Michael T Collins, Leonid V Chernomordik
RESUMO

Multinucleated osteoclasts, essential for skeletal remodeling in health and disease, are formed by the fusion of osteoclast precursors, where each fusion event raises their bone-resorbing activity. Here we show that the nuclear RNA chaperone, La protein has an additional function as an osteoclast fusion regulator. Monocyte-to-osteoclast differentiation starts with a drastic decrease in La levels. As fusion begins, La reappears as a low molecular weight species at the osteoclast surface, where it promotes fusion. La's role in promoting osteoclast fusion is independent of canonical La-RNA interactions and involves direct interactions between La and Annexin A5, which anchors La to transiently exposed phosphatidylserine at the surface of fusing osteoclasts. Disappearance of cell-surface La, and the return of full length La to the nuclei of mature, multinucleated osteoclasts, acts as an off switch of their fusion activity. Targeting surface La in a novel explant model of fibrous dysplasia inhibits excessive osteoclast formation characteristic of this disease, highlighting La's potential as a therapeutic target.

MATERIAIS
Número do produto
Marca
Descrição do produto

Sigma-Aldrich
Anti-DC-STAMP Antibody, clone 1A2, clone 1A2, from mouse