TRPM7 functions in non-neuronal and neuronal systems: Perspectives on its role in the adult brain.

Abstract Transient receptor potentialmelastatin-like 7 ( TRPM7) has a unique dual protein structure. It is an ion channel that has biophysical characteristics enabling divalent cations transport and a kinase domain involved in molecular events starting from modulating signaling pathways to inducing chromatin remodeling. Over the past 15 years, significant progress in the molecular and functional characterization of TRPM7has been made in peripheral tissue and/or cell lines. TRPM7appears to be involved in a plethora of physiological and pathological processes including embryonic development, organogenesis, cell proliferation and survival, and cell death following certain triggers. In the post-mitotic neuronal cells, however, the functional role of TRPM7remains unclear. Majority of the progress in this area of research has focused on the potential role of TRPM7in mediating neuronal death following ischemia-like and neuronal injuries-like conditions. Here, we summarize major progress on the biological roles of the TRPM7during development and in mitotic systems (cell lines). Then, we address the recent developments made in neuronal systems. Besides its role in neuronal death, we emphasize on direct and indirect evidences that could link TRPM7to fundamental neurobiological processes such as synaptic transmission, synapse remodeling, plasticity, cognitive functions as well as to some mental disorders. Therefore, we propose that an equivalent effort is demanded to systematically characterize the role of TRPM7in healthy neural system before presentingit as a potential molecular target to treat neurodegenerative disorders or to prevent neuronal death following ischemia and/or neuronal injuries.