title: Cytoplasmic hnRNPK interacts with GSK3β and is essential for the osteoclast differentiation.
abstract: Osteoclast differentiation is a complex and finely regulated physiological process that involves a variety of signaling pathways and factors. Recent studies suggested that the Ser9 phosphorylation of Glycogen synthase kinase-3β (GSK3β) is required for the osteoclast differentiation. However, the precise underlying mechanism remains unclear. We have previously identified the heterogeneous nuclear ribonucleoprotein K (hnRNPK) as a putative GSK3β interactor. In the present study, we demonstrate that, during the RANKL-induced osteoclast differentiation, the PI3K/Akt-mediated Ser9 phosphorylation of GSK3β provokes the nuclear-cytoplasmic translocation of hnRNPK in an ERK-dependent manner, enhancing the cytoplasmic co-localization and interaction of GSK3β and hnRNPK. We show that hnRNPK is essential for the osteoclast differentiation, and is involved in several reported functions of GSK3β, including the activation of NF-κB, the expression of NFATc1, and the acetylation of tubulin, all known to be critical for osteoclast differentiation and functions. We find that hnRNPK is localized in the actin belt, and is important for the mature osteoclast formation. Taken together, we demonstrate here the critical role of hnRNPK in osteoclast differentiation, and depict a model in which the cytoplasmic hnRNPK interacts with GSK3β and regulates its function.
authors.affiliation: Key laboratory of functional protein research of Guangdong higher education institutes, Institute of life and health engineering, Jinan University, Guangzhou, 510632, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Fan
authors.affiliation: Key laboratory of functional protein research of Guangdong higher education institutes, Institute of life and health engineering, Jinan University, Guangzhou, 510632, China.
authors.forename: Haiting
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Key laboratory of functional protein research of Guangdong higher education institutes, Institute of life and health engineering, Jinan University, Guangzhou, 510632, China.
authors.forename: Jinmei
authors.initials: J
authors.lastname: Wei
authors.affiliation: Key laboratory of functional protein research of Guangdong higher education institutes, Institute of life and health engineering, Jinan University, Guangzhou, 510632, China.
authors.forename: Xuejuan
authors.initials: X
authors.lastname: Gao
authors.affiliation: Key laboratory of functional protein research of Guangdong higher education institutes, Institute of life and health engineering, Jinan University, Guangzhou, 510632, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Key laboratory of functional protein research of Guangdong higher education institutes, Institute of life and health engineering, Jinan University, Guangzhou, 510632, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key laboratory of functional protein research of Guangdong higher education institutes, Institute of life and health engineering, Jinan University, Guangzhou, 510632, China.
authors.forename: Gong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Key laboratory of functional protein research of Guangdong higher education institutes, Institute of life and health engineering, Jinan University, Guangzhou, 510632, China.
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: He
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth, 6009, Western Australia, Australia.
authors.forename: Jiake
authors.initials: J
authors.lastname: Xu
authors.affiliation: Key laboratory of functional protein research of Guangdong higher education institutes, Institute of life and health engineering, Jinan University, Guangzhou, 510632, China.
authors.forename: Langxia
authors.initials: L
authors.lastname: Liu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D057809:HEK293 Cells; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000378:metabolism*; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D053245:RANK Ligand / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D014404:Tubulin / Q000378:metabolism
chemical_list: D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D053245:RANK Ligand; D014404:Tubulin; D010768:Phosphoserine; D019869:Phosphatidylinositol 3-Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride