TMEM33调节肾小管上皮细胞的细胞内钙稳态。,Nature Communications

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TMEM33调节肾小管上皮细胞的细胞内钙稳态。
Nature Communications ( IF 14.7 ) Pub Date : 2019-05-02 , DOI: 10.1038/s41467-019-10045-y
Malika Arhatte ₁ , Gihan S Gunaratne ₂ , Charbel El Boustany ₁ , Ivana Y Kuo ₃ , Céline Moro ₁ , Fabrice Duprat ₁ , Magali Plaisant ₁ , Hélène Duval ₁ , Dahui Li ₄ , Nicolas Picard ₅ , Anais Couvreux ₁ , Christophe Duranton ₆ , Isabelle Rubera ₆ , Sophie Pagnotta ₇ , Sandra Lacas-Gervais ₇ , Barbara E Ehrlich ₈ , Jonathan S Marchant ₉ , Aaron M Savage _{10,

11} , Fredericus J M van Eeden _{11,

12} , Robert N Wilkinson _{10,

11} , Sophie Demolombe ₁ , Eric Honoré ₁ , Amanda Patel ₁

Affiliation

Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut national de la santé et de la recherche médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST, Valbonne, 06560, France.
Department of Pharmacology, University of Minnesota, Minneapolis, MN, 55455, USA.
Cell and Molecular Physiology Stritch School of Medicine Loyola University Chicago, Maywood, IL, 60153, USA.
The State Key Laboratory of Pharmaceutical Biotechnology, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China.
Laboratory of Tissue Biology and Therapeutic Engineering, UMR 5305 CNRS, University Lyon 1, Lyon, 69367, France.
Université Côte d'Azur, LP2M CNRS-UMR7370, Labex ICST, Medical Faculty, Nice, 06108, France.
CCMA UFR Sciences, Université Côte d'Azur, Nice, 06108, France.
Department of Pharmacology, School of Medicine, Yale University, New Haven, CT, 06520-8066, USA.
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, S102TN, UK.
The Bateson Centre, University of Sheffield, Sheffield, S102TN, UK.
Department of Biomedical Science, University of Sheffield, Sheffield, S102TN, UK.

多囊藻毒素中的突变会导致常染色体显性多囊肾疾病（ADPKD）。在这里，我们显示跨膜蛋白33（TMEM33）与内质网（ER）膜上的离子通道多囊藻蛋白2（PC2）相互作用，从而增强了在与平面双层膜融合的ER脂质体中整个生理钙范围内的开放度。因此，TMEM33以PC2依赖性方式降低细胞内钙含量，削弱溶酶体钙的重新填充，引起组织蛋白酶移位，抑制内质网应激时自噬通量，以及对细胞凋亡的敏感性。小鼠中TMEM33的失效为肾脏ER应激提供了有效的保护。相比之下，TMEM33不会影响斑马鱼中pkd2依赖的肾囊肿的发生。一起，

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更新日期：2019-05-16

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