Effect of the CALHM1 G330D and R154H Human Variants on the Control of Cytosolic Ca2+ and Aβ Levels
作者： Valérie Vingtdeux , Jessica E. Tanis , Pallavi Chandakkar , Haitian Zhao , Ute Dreses-Werringloer
DOI: 10.1371/JOURNAL.PONE.0112484
关键词:
摘要: CALHM1 is a plasma membrane voltage-gated Ca2+-permeable ion channel that controls amyloid-β (Aβ) metabolism and potentially involved in the onset of Alzheimer's disease (AD). Recently, Rubio-Moscardo et al. (PLoS One (2013) 8: e74203) reported identification two variants, G330D R154H, early-onset AD (EOAD) patients. The authors provided evidence these human variants were rare resulted complete loss function. Recent publicly available large-scale exome sequencing data confirmed R154H variant (minor allele frequency (MAF) = 0.015%), but not (MAF = 3.5% an African American cohort). Here, we show both exhibited gating permeation properties indistinguishable from wild-type when expressed Xenopus oocytes. While there was also no effect mutation on Ca2+ uptake by transfected mammalian cells, associated with defects control Aβ levels this cell system. Together, our frequent has obvious functional consequences therefore unlikely to contribute EOAD. Our demonstrate interferes cytosolic accumulation. results strengthen notion influences metabolism, further investigation will be required determine whether or other natural CALHM1, is/are
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