RECS1 deficiency in mice induces susceptibility to cystic medial degeneration

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  • Zhao Hanjun
    Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University
  • Ito Akihiko
    Division of Surgical Pathology, Graduate School of Medicine, Kobe University
  • Kimura Shinya H.
    Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University
  • Yabuta Norikazu
    Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University
  • Sakai Naohiko
    Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University
  • Ikawa Masahito
    Genome Information Research Center, Osaka University
  • Okabe Masaru
    Genome Information Research Center, Osaka University
  • Matsuzawa Yuji
    Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University
  • Yamashita Shizuya
    Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University
  • Nojima Hiroshi
    Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University

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RECS1 is a novel shear stress-responsive gene that encodes a protein putatively forming seven-span transmembrane domains. We reports here that mouse RECS1 (mRECS1) transcripts is detected in most tissues except for thymus, spleen and testis. The putative cytoplasmic N-terminus of mRECS1 has a high content of proline (23%) and glycine (12%) residues, contains one PPXY motif, multiple PXXP motifs and one overlapping P(T/S)AP and PPXY motif (P(T/S)APPXY). The PPXY motif lies within one potential PEST sequence (PEST score: +7.65). We prepared anti-RECS1 polyclonal antibody and found by western blot analysis that the mRECS1 protein in the lung and aorta was detected as a 34.4 kDa band. However, one shifted 58 kDa band or three shifted bands (48, 69, 82 kDa) were detected in the heart or the liver, respectively. Since northern blot detected only one species of mRECS1 mRNA in heart and liver tissues, as well as other tissues (~2.2 kb), these differences in molecular weight seem to be due to posttranslational modification. Biochemical fractionation and RECS1-GFP fusion protein revealed that RECS1 localizes at the endosomal/lysosomal membranes in the cytoplasm. To understand the function of RECS1 in the body, we made RECS1 knockout (KO) mice and found that RECS1 KO mice (older than 14 months) are prone to cystic medial degeneration (CMD). Taken together, we conclude that RECS1 is an endosomal/lysosomal membrane protein which plays protective roles in vascular remodeling.<br>

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