ORIGINAL ARTICLE

Cell Research (2006)16: 337-346
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Isolation and characterization of Xenopus laevis homologs of the mouse inv gene and functional analysis of the conserved calmodulin binding sites

Yukuto Yasuhiko, Koichiro Shiokawa, Toshio Mochizuki, Makoto Asashima, Takahiko Yokoyama

Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Department of Medicine, Kidney Center, Tokyo Women’s Medical University, School of Medicine, Japan; Department of Life Science, University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 158-8902, Japan; Department of Anatomy and Developmental Biology, Tokyo Women’s Medical College, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan

Correspondence: Takahiko Yokoyama Department of Anatomy, Kyoto Prefecture University of Medicine, 465 Kajiicho,Hirokoji- agaru, Kawaramachi-dori, Kamikyo-ku, 602-0841, Japan Tel: 81-75-251-5303; Fax: 81-75-251-5304; E-mail: tyoko@koto.kpu-m.ac.jp *Present addresses: Yukuto Yasuhiko1, Koichiro Shiokawa2, Toshio Mochizuki3 Cellular and Molecular Toxicology Division, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan Department of Biosciences, School of Science and Engineering, Teikyou University, 1-1 Toyosatodai, Utsunomiya-city, Tochigi prefecture 320-8551,Japan Department of Medicine II, Hokkaido University Graduate School of Medicine,Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan Received 1 Oct 2005 ; revised 14 Nov 2005; accepted 6 Dec 2005, published online 13 Apr 2006

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The homozygous inv (inversion of embryonic turning) mouse mutant shows situs inversus and polycystic kidney disease, both of which result from the lack of the inv gene. Previously, we suggested that inv may be important for the left–right axis formation, not only in mice but also in Xenopus, and that calmodulin regulates this inv protein function. Here, we isolated and characterized two Xenopus laevis homologs (Xinv-1 and Xinv-2) of the mouse inv gene, and performed functional analysis of the conserved IQ motifs that interact with calmodulin. Xinv-1 expresses early in development in the same manner as mouse inv does. Unexpectedly, a full-length Xenopus inv mRNA did not randomize cardiac orientation when injected into Xenopus embryos, which is different from mouse inv mRNA. Contrary to mouse inv mRNA, Xenopus inv mRNA with mutated IQ randomized cardiac orientation. The present study indicates that calmodulin binding sites (IQ motifs) are crucial in controlling the biological activity of both mouse and Xenopus inv proteins. Although mouse and Xenopus inv genes have a quite similar structure, the interaction with calmodulin and IQ motifs of Xenopus inv and mouse inv proteins may regulate their function in different ways.

Cell Research (2006) 16:337-346. doi:10.1038/sj.cr.7310044; published online 13 April 2006

Keywords: Left–right asymmetry, inv, calmodulin, ankyrin, IQ motif, Xenopus, calcium