Abstract
Transient receptor potential cation channel subfamily M member 7 (TRPM7) is a bi-functional protein comprising a TRP ion channel segment linked to an α-type protein kinase domain. Genetic inactivation of TRPM7 revealed its central role in magnesium metabolism, cell motility, proliferation and differentiation. TRPM7 is associated with anoxic neuronal death, cardiac fibrosis and tumor progression highlighting TRPM7 as a new drug target. Recently, several laboratories have independently identified pharmacological compounds inhibiting or activating the TRPM7 channel. The recently found TRPM7 modulators were used as new experimental tools to unravel cellular functions of the TRPM7 channel. Here, we provide a concise overview of this emerging field.
Highlights
Transient receptor potential cation channel subfamily M member 7 (TRPM7) is a bi-functional protein comprising a transient receptor potential (TRP) ion channel segment linked to an α-type protein kinase domain
Only TRPM7 and its homologous protein TRPM6 are known as channels covalently fused to kinase domains [1,6,7,8,9,10,11]
Mutations S138L and P1040R correspond to TRPM6 missense mutations causing an inherited disorder in humans known as hypomagnesemia and secondary hypocalcemia (HSH)
Summary
TRPM7 is a plasma membrane protein that contains a transmembrane ion channel segment linked to a cytosolic α-type serine/threonine protein kinase domain as illustrated in Figure 1 [1,2,3,4,5]. The physiological relevance of these findings remains to be elucidated Along these lines, Kaitsuka et al [23] have recently shown that mice carrying a point mutation in the catalytic site of the TRPM7 kinase domain (‘kinase-dead’ knock-in mutation, Figure 1) display an unaltered lifespan as well as normal Ca2+ and. Hofmann et al have shown recently that the TRP domain plays a key role in Mg2+ dependent gating of TRPM7 since a point mutation of a conserved serine residue in the TRP domain (Figure 1) is sufficient to create a constitutively active. Xie et al [22] reported that neutralization of basic residues in the TRP domain (Figure 1) leads to non-functional or dysfunctional TRPM7 with dampened regulation by PIP2 suggesting that the TRP domain may interact with PIP2
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