Unlocking TRPM7 interactions: A database-driven quest

Transient receptor potential cation channel subfamily M member 7 (TRPM7) is a dual function protein comprising a non-selective cation channel and an atypical kinase domain. TRPM7 has been involved in many diseases including malignancies. Indeed, TRPM7 is proposed as a promising target for therapeutical drug design. Numerous studies have shown that TRPM7 interacts with proteins involved in regulating intracellular signaling. Therefore, a better understanding of the TRPM7 interactome would provide insight into pathophysiological mechanisms at the cellular and molecular levels. It could also open up new therapeutic avenues for molecules targeting either the proteins of interest directly or protein-protein interactions. In the first part of this work, we present the interaction partners described in the literature for TRPM7 and their potential impacts on cell biology. In the second part of the manuscript, we use public databases and protein interaction modeling tools to characterize the TRPM7 interactome. In particular, the analysis of the TRPM7 interactome using experimental data (BioGRID) and modeling tools (ProteinPrompt) has allowed us to isolate 19 genes of interest mainly related to small GTPase pathways involved in digestive neoplasia such as colorectal and pancreatic cancers. In summary, we provide an extended overview of potential TRPM7 interactors which need to be validated in cellular models. This will provide crucial insights into the molecular mechanisms at the tumor cell membrane, helping us to propose new therapeutic targets for precision medicine.