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Cooperative function of the CHD5-like protein Mdm39p with a P-type ATPase Spf1p in the maintenance of ER homeostasis in Saccharomyces cerevisiae

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Abstract

Spf1p is a P-type ATPase that is mainly localized to the endoplasmic reticulum (ER) in Saccharomyces cerevisiae. The protein is involved in the maintenance of ion homeostasis in the ER. To investigate the intracellular role of Spf1p in more detail, we performed a genetic screen for mutations that lead to synthetic lethality in combination with a disruption of SPF1; the mutations identified have been termed lws (for lethal with spf1) mutations. Mutant alleles of five LWS genes (MDM39, RIC1, LAS21, TUP1 and BTS1) were recovered. The identification of these genes provides clues to the physiological relationships between Spf1p function and the secretory pathway. Among the five genes identified, MDM39 encodes a membrane protein that is similar to the protein CHD5/WRB, which is involved in the pathogenesis of Down syndrome-associated congenital heart disease in humans. We localized Mdm39p to the ER. The Δmdm39 mutant exhibited defects in glycosylation, cell wall organization and the unfolded protein response. It also showed calcium-related phenotypes and synthetic lethal interactions with deletion mutations in other LWS genes. Our findings imply a homeostatic role for Mdm39p, which may be related to the regulation of calcium ion fluxes in the ER, and is indispensable for mutants that lack Spf1p.

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Acknowledgements

This work was supported in part by the Cooperative System for Supporting Priority Research of the Japan Science and Technology Agency. We thank Dr K. Isono for providing yeast strains, Dr Y. Ohya for providing the yeast genomic library, Drs. R.D. Gietz, J.H. Hegemann, K. Mori, Y. Noda and E. Schiebel for providing plasmids, Dr M. Tokunaga for providing antibodies, and Dr J. Shima for participating in critical discussions.

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  1. National Food Research Institute, 2-1-12 Kannondai, Tsukuba, Ibaraki, 305-8642, Japan

    A. Ando & C. Suzuki

  2. National Institute of Livestock and Grassland Science, 2 Ikenodai, Tsukuba, Ibaraki, 305-0901, Japan

    C. Suzuki

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  1. A. Ando
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  2. C. Suzuki
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Correspondence to C. Suzuki.

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Communicated by D. Thomas

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Ando, A., Suzuki, C. Cooperative function of the CHD5-like protein Mdm39p with a P-type ATPase Spf1p in the maintenance of ER homeostasis in Saccharomyces cerevisiae. Mol Genet Genomics 273, 497–506 (2005). https://doi.org/10.1007/s00438-005-1153-6

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  • DOI: https://doi.org/10.1007/s00438-005-1153-6

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