Identification and lateral membrane localization of cyclin M3, likely to be involved in renal Mg2+ handling in seawater fish

Zinia Islam, Naoko Hayashi, Hana Inoue, Takahiro Umezawa, Yuuri Kimura, Hiroyuki Doi, Michael F. Romero, Shigehisa Hirose, Akira Kato

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


The kidney of marine teleosts isthe major site of Mg2 excretion and produces urine with a highMg2+ concentration. However, the transporters involved in Mg2+ excretion are poorly understood. The cyclin M (Cnnm; also known as ancient conserved domain protein) family comprises membrane pro-teins homologous to the bacterial Mg2+ and Co2+ efflux protein, CorC. To understand the molecular mechanism of Mg2+ homeostasis in marine teleosts, we analyzed the expression of the Cnnm family genes in the seawater (SW) pufferfish, torafugu (Takifugu rubripes), and the closely related euryhaline species, mefugu (Takifugu obscurus). Database mining and phylogenetic analysis indicated that the Takifugu genome contains six members of the Cnnm family: two orthologs of Cnnm1, one of Cnnm2, one of Cnnm3, and two of Cnnm4. RT-PCR analyses indicated that Cnnm2, Cnnm3, and Cnnm4a are expressed in the kidney, whereas other members are mainly expressed in the brain. Renal expression of Cnnm3 was upregulated in SW mefugu, whereas renal expression of Cnnm2 was upregulated in freshwater (FW) mefugu. No significant difference was observed in renal expression of Cnnm4a between SW and FW mefugu. In situ hybridization and immunohistochemical analyses of the SW mefugu kidney revealed that Cnnm3 is expressed in the proximal tubule, and its product localizes to the lateral membrane. When Cnnm3 wasexpressed in Xenopus laevis oocytes, whole cellular Mg2+ contentand free intracellular Mg2+ activity significantly decreased. Theseresults suggest that Cnnm3 is involved in body fluid Mg2+ homeostasis in marine teleosts.

Original languageEnglish (US)
Pages (from-to)R525-R537
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number5
StatePublished - Sep 1 2014


  • Lateral membrane
  • Magnesium homeostasis
  • Marine teleost
  • Proximal tubule

ASJC Scopus subject areas

  • General Medicine


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