Abstract：
:Guamanian amyotrophic lateral sclerosis (ALS-G) and parkinsonism dementia (PD-G) have been epidemiologically linked to an environment severely deficient in calcium (Ca2+) and magnesium (Mg2+). Transient receptor potential melastatin 7 (TRPM7) is a bifunctional protein containing both channel and kinase domains that has been proposed to be involved in the homeostatic regulation of intracellular Ca2+, Mg2+, and trace metal ion concentration. There is evidence that TRPM7 is constitutively active and that the number of available channels is dependent on intracellular free Mg2+ levels. We found a TRPM7 variant in a subset of ALS-G and PD-G patients that produces a protein with a missense mutation, T1482I. Recombinant T1482I TRPM7 exhibits the same kinase catalytic activity as WT TRPM7. However, heterologously expressed T1482I TRPM7 produces functional channels that show an increased sensitivity to inhibition by intracellular Mg2+. Because the incidence of ALS-G and PD-G has been associated with prolonged exposure to an environment severely deficient in Ca2+ and Mg2+, we propose that this variant TRPM7 allele confers a susceptibility genotype in such an environment. This study represents an initial attempt to address the important issue of gene-environment interactions in the etiology of these diseases.
journal_name
Proc Natl Acad Sci U S Aauthors
Hermosura MC,Nayakanti H,Dorovkov MV,Calderon FR,Ryazanov AG,Haymer DS,Garruto RMdoi
10.1073/pnas.0505149102keywords:
subject
Has Abstractpub_date
2005-08-09 00:00:00pages
11510-5issue
32eissn
0027-8424issn
1091-6490pii
0505149102journal_volume
102pub_type
杂志文章abstract：:RNAs 1 and 2 of the tripartite cowpea chlorotic mottle virus (CCMV) genome are sufficient for RNA replication in protoplasts, whereas systemic infection of cowpea plants additionally requires RNA3, which encodes the 3a noncapsid protein and coat protein. By using biologically active CCMV cDNA clones, we find that dele...
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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doi：10.1073/pnas.93.20.11126
更新日期：1996-10-01 00:00:00
