Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia
Vladimir Chubanov,Siegfried Waldegger,Michael Mederos y Schnitzler,Helga Vitzthum,Martin Sassen,Hannsjörg W. Seyberth,Martin Konrad,Thomas Gudermann +7 more
TLDR
The naturally occurring S141L TRPM 6 missense mutation abrogated the oligomeric assembly of TRPM6, thus providing a cell biological explanation for the human disease.Abstract:
Impaired magnesium reabsorption in patients with TRPM6 gene mutations stresses an important role of TRPM6 (melastatin-related TRP cation channel) in epithelial magnesium transport. While attempting to isolate full-length TRPM6, we found that the human TRPM6 gene encodes multiple mRNA isoforms. Full-length TRPM6 variants failed to form functional channel complexes because they were retained intracellularly on heterologous expression in HEK 293 cells and Xenopus oocytes. However, TRPM6 specifically interacted with its closest homolog, the Mg2+-permeable cation channel TRPM7, resulting in the assembly of functional TRPM6/TRPM7 complexes at the cell surface. The naturally occurring S141L TRPM6 missense mutation abrogated the oligomeric assembly of TRPM6, thus providing a cell biological explanation for the human disease. Together, our data suggest an important contribution of TRPM6/TRPM7 heterooligomerization for the biological role of TRPM6 in epithelial magnesium absorption.read more
Citations
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Journal ArticleDOI
An Introduction to TRP Channels
TL;DR: The aim of this review is to provide a basic framework for understanding the function of mammalian transient receptor potential (TRP) channels, particularly as they have been elucidated in heterologous expression systems.
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Transient Receptor Potential Cation Channels in Disease
TL;DR: An overview of the impact of TRP channels on the pathogenesis of several diseases is provided and several TRPs for which a causal pathogenic role might be anticipated are identified.
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The TRP Superfamily of Cation Channels
TL;DR: Members of the TRP superfamily function in various processes, although their roles are best established in sensory modalities ranging from vision to hearing, taste, pheromone detection, pain perception, and osmosensation, which have relevance for human health.
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TRP channels: an overview.
TL;DR: The present review summarizes the most pertinent recent evidence regarding the structural and functional properties of TRP channels, focusing on the regulation and physiology of mammalian TRPs.
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The functional network of ion channels in T lymphocytes
TL;DR: The expression pattern of Ca2+ and K+ channels and hence the functional network can adapt depending upon the state of differentiation and activation, and this allows for different stages of an immune response to be targeted specifically.
References
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Journal ArticleDOI
TRP channels as cellular sensors
TL;DR: TRP channels are the vanguard of the authors' sensory systems, responding to temperature, touch, pain, osmolarity, pheromones, taste and other stimuli, but their role is much broader than classical sensory transduction.
Journal ArticleDOI
LTRPC7 is a Mg·ATP-regulated divalent cation channel required for cell viability
Monica J. S. Nadler,Meredith C. Hermosura,Kazunori Inabe,Anne-Laure Perraud,Qiqin Zhu,Alexander J. Stokes,Tomohiro Kurosaki,Jean-Pierre Kinet,Reinhold Penner,Andrew M. Scharenberg,Andrew M. Scharenberg,Andrea Fleig +11 more
TL;DR: The data indicate that LTRPC7, by virtue of its sensitivity to physiological Mg·ATP levels, may be involved in a fundamental process that adjusts plasma membrane divalent cation fluxes according to the metabolic state of the cell.
Journal ArticleDOI
TRPC1 and TRPC5 form a novel cation channel in mammalian brain.
TL;DR: It is demonstrated here that TRPC1 and TRPC5 are subunits of a heteromeric neuronal channel, and proposed that many TRPC heteromers form diverse receptor-regulated nonselective cation channels in the mammalian brain.
Journal ArticleDOI
Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family.
Karl P. Schlingmann,Stefanie Weber,Melanie Peters,Lene N. Nejsum,Helga Vitzthum,Karin Klingel,Markus Kratz,Elie Haddad,Ellinor Ristoff,Dganit Dinour,Maria Syrrou,Søren Nielsen,Martin Sassen,Siegfried Waldegger,Hannsjörg W. Seyberth,Martin Konrad +15 more
TL;DR: Findings indicate that TRPM6 is crucial for magnesium homeostasis and implicate a TRPM family member in human disease, and are associated with autosomal-recessive hypomagnesemia with secondary hypocalcemia.
Journal ArticleDOI
Subunit composition of mammalian transient receptor potential channels in living cells
TL;DR: This work investigates the combinatorial rules of TRPC assembly by pursuing four independent experimental approaches and shows that TRPC2 does not interact with any known TRPC protein andTRPC1 has the ability to form channel complexes together with TRPC4 and TRPC5.