| First Author | Sato Y | Year | 2011 |
| Journal | Cell Biosci | Volume | 1 |
| Issue | 1 | Pages | 7 |
| PubMed ID | 21711689 | Mgi Jnum | J:262208 |
| Mgi Id | MGI:6161930 | Doi | 10.1186/2045-3701-1-7 |
| Citation | Sato Y, et al. (2011) Extracellular domain of CD98hc is required for early murine development. Cell Biosci 1(1):7 |
| abstractText | BACKGROUND: The multifunctional protein CD98 heavy chain (CD98hc, Slc3a2) associates with integrin beta1 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 beta1-null mice, supporting the importance of its interaction with integrin beta1. 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. RESULTS: In this study, mice were generated from embryonic stem (ES) cell line (PST080) harboring a mutant CD98hc allele (CD98hcDelta/+). Expression of the CD98hc mutant allele results in DeltaCD98hc-beta geo fusion protein where extracellular C-terminal 102 amino acids of CD98hc are replaced with beta geo. Analyses of PST080 ES cells as well as reconstituted frog oocytes demonstrated that DeltaCD98hc-beta geo fusion protein preserved its ability to interact with integrin beta1 although this mutant protein was hardly localized on the cell surface. These findings suggest that DeltaCD98hc-beta geo protein can mediate integrin signaling but cannot support amino acid transport through LATs. CD98hcDelta/+ 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, CD98hcDelta/Delta embryos are likely to die between E7.5 and E9.5. CONCLUSIONS: Considering 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. |
