Dataset Information

Conditional deletion of CD98hc inhibits osteoclast development.

ABSTRACT: The CD98 heavy chain (CD98hc) regulates virus-induced cell fusion and monocyte fusion, and is involved in amino acid transportation. Here, we examined the role that CD98hc plays in the formation of osteoclasts using CD98hc^flox/floxLysM-cre peritoneal macrophages (CD98hc-defect macrophages). Peritoneal macrophages were stimulated with co-cultured with osteoblasts in the presence of 1,25(OH)² vitamin D₃, and thereafter stained with tartrate-resistant acid phosphatase staining solution. The multinucleated osteoclast formation was severely impaired in the peritoneal macrophages isolated from the CD98hc^-defect mice compared with those from wild-type mice. CD98hc mediates integrin signaling and amino acid transport through the CD98 light chain (CD98lc). In integrin signaling, suppression of the M-CSF-RANKL-induced phosphorylation of ERK, Akt, JNK and p130Cas were observed at the triggering phase in the CD98h-defect peritoneal macrophages. Moreover, we showed that the general control non-derepressible (GCN) pathway, which was activated by amino acid starvation, was induced by the CD98hc-defect peritoneal macrophages stimulated with RANKL. These results indicate that CD98 plays two important roles in osteoclast formation through integrin signaling and amino acid transport.

SUBMITTER: Tsumura H

PROVIDER: S-EPMC5600448 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Conditional deletion of CD98hc inhibits osteoclast development.

Tsumura Hideki H Ito Morihiro M Takami Masamichi M Arai Miyuki M Li Xiao-Kang XK Hamatani Toshio T Igarashi Arisa A Takada Shuji S Miyado Kenji K Umezawa Akihiro A Ito Yasuhiko Y

Biochemistry and biophysics reports 20151202

The CD98 heavy chain (CD98hc) regulates virus-induced cell fusion and monocyte fusion, and is involved in amino acid transportation. Here, we examined the role that CD98hc plays in the formation of osteoclasts using CD98hcflox/floxLysM-cre peritoneal macrophages (CD98hc-defect macrophages). Peritoneal macrophages were stimulated with co-cultured with osteoblasts in the presence of 1,25(OH)2 vitamin D3, and thereafter stained with tartrate-resistant acid phosphata ...[more]

PMID: 28955825

Similar Datasets

Project description:BackgroundThe multifunctional protein CD98 heavy chain (CD98hc, Slc3a2) associates with integrin ?1 through its cytoplasmic and transmembrane domains and the CD98hc-mediated integrin signaling is required for maintenance of ES cell proliferation. CD98hc-null mice exhibit early post-implantation lethality similar to integrin ?1-null mice, supporting the importance of its interaction with integrin ?1. On the other hand, the extracellular domain of CD98hc interacts with L-type amino acid transporters (LATs) and is essential for appropriate cell surface distribution of LATs. LATs mediate the transport of amino acids and other molecules such as thyroid hormone. In this respect, CD98hc may also affect development via these transporters.ResultsIn this study, mice were generated from embryonic stem (ES) cell line (PST080) harboring a mutant CD98hc allele (CD98hc?/+). Expression of the CD98hc mutant allele results in ?CD98hc-? geo fusion protein where extracellular C-terminal 102 amino acids of CD98hc are replaced with ? geo. Analyses of PST080 ES cells as well as reconstituted frog oocytes demonstrated that ?CD98hc-? geo fusion protein preserved its ability to interact with integrin ?1 although this mutant protein was hardly localized on the cell surface. These findings suggest that ?CD98hc-? geo protein can mediate integrin signaling but cannot support amino acid transport through LATs. CD98hc?/+ mice were normal. Although some of the implantation sites lacked embryonic component at E9.5, all the implantation sites contained embryonic component at E7.5. Thus, CD98hc?/? embryos are likely to die between E7.5 and E9.5.ConclusionsConsidering that CD98hc complete knockout (CD98hc-/-) embryos are reported to die shortly after implantation, our findings suggest potential stage-specific roles of CD98hc in murine embryonic development. CD98hc may be essential for early post-implantation development by regulating integrin-dependent signaling, while the other function of CD98hc as a component of amino acid transporters may be required for embryonic development at later stages.

Dataset Information

Conditional deletion of CD98hc inhibits osteoclast development.

Publications

Conditional deletion of CD98hc inhibits osteoclast development.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets