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TRPM7 is a polypeptide with intrinsic ion channel and protein kinase domains whose targeted deletion causes cells to experience growth arrest within 24 hr and eventually die. Here, we show that while TRPM7's kinase domain is not essential for activation of its channel, a functional coupling exists such that structural alterations of the kinase domain alter(More)
TRPM7 and its closest homologue, TRPM6, are the only known fusions of an ion channel pore with a kinase domain. Deletion of TRPM7 in DT40 B-lymphocytes causes growth arrest, Mg(2+) deficiency, and cell death within 24-48 h. Amazingly, in analogy to TRPM6-deficient patients who can live a normal life if provided with a Mg(2+)-rich diet, TRPM7-deficient DT40(More)
TRPM2 is a member of the transient receptor potential melastatin-related (TRPM) family of cation channels, which possesses both ion channel and ADP-ribose hydrolase functions. TRPM2 has been shown to gate in response to oxidative and nitrosative stresses, but the mechanism through which TRPM2 gating is induced by these types of stimuli is not clear. Here we(More)
Two related neurodegenerative disorders, Western Pacific amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD), originally occurred at a high incidence on Guam, in the Kii peninsula of Japan, and in southern West New Guinea more than 50 years ago. These three foci shared a unique mineral environment characterized by the presence of severely low(More)
The transient receptor potential melastatin member 7 (TRPM7) and member 6 (TRPM6) are divalent cation channel kinases essential for magnesium (Mg(2+)) homeostasis in vertebrates. It remains unclear how TRPM6 affects divalent cation transport and whether this involves functional homomeric TRPM6 plasma membrane channels or heteromeric channel assemblies with(More)
TRPM2 is a recently identified TRPM family cation channel which is unique among known ion channels in that it contains a C-terminal domain which is homologous to the NUDT9 ADP-ribose hydrolase and possesses intrinsic ADP-ribose hydrolase activity. Here, available information on the TRPM2 gene, transcripts, predicted protein products, and assembled(More)
PLC-isozymes are central elements of cellular signaling downstream of numerous receptors. PLCγ2 is a pivotal component of B cell receptor (BCR) signaling. The regulation of PLCγ2-dependent signaling functions by Tyr-phosphorylation is well characterized, however, the potential role of Ser/Thr phosphorylation events remains undefined. TRPM7 is the fusion of(More)
In just a few years, the discovery and subsequent characterization of several members of the TRPM family of cation channels have provided us with surprising new insights into unknown aspects of cellular ion-homeostasis regulation. This includes reports about ADP-ribose functioning as a novel intracellular second messenger and gating molecule of the(More)
Magnesium (Mg(2+)) transport across membranes plays an essential role in cellular growth and survival. TRPM7 is the unique fusion of a Mg(2+) permeable pore with an active cytosolic kinase domain, and is considered a master regulator of cellular Mg(2+) homeostasis. We previously found that the genetic deletion of TRPM7 in DT40 B cells results in Mg(2+)(More)
Over the past decades, the clinical relevance and biological significance of Mg2+ have been thoroughly documented. Although multiple Mg2+-transport pathways have been biophysically characterized, the molecular identity of the postulated components of Mg2+-homeostasis regulation in vertebrates remain undefined. Recent advances in the fields of genetics,(More)