PRL-1/2 phosphatases control TRPM7 magnesium-dependent function to regulate cellular bioenergetics.

Phosphatases of regenerating liver (PRL-1, PRL-2, PRL-3; also known as PTP4A1, PTP4A2, PTP4A3, respectively) control intracellular magnesium levels by interacting with the CNNM magnesium transport regulators. Still, the exact mechanism governing magnesium transport by this protein complex is not well understood. Herein, we have developed a genetically encoded intracellular magnesium-specific reporter and demonstrate that the CNNM family inhibits the function of the TRPM7 magnesium channel. We show that the small GTPase ARL15 increases CNNM3/TRPM7 protein complex formation to reduce TRPM7 activity. Conversely, PRL-2 overexpression counteracts ARL15 binding to CNNM3 and enhances the function of TRPM7 by preventing the interaction between CNNM3 and TRPM7. Moreover, while TRPM7-induced cell signaling is promoted by PRL-1/2, it is reduced when CNNM3 is overexpressed. Lowering cellular magnesium levels reduces the interaction of CNNM3 with TRPM7 in a PRL-dependent manner, whereby knockdown of PRL-1/2 restores the protein complex formation. Cotargeting of TRPM7 and PRL-1/2 alters mitochondrial function and sensitizes cells to metabolic stress induced by magnesium depletion. These findings reveal the dynamic regulation of TRPM7 function in response to PRL-1/2 levels, to coordinate magnesium transport and reprogram cellular metabolism.

Systematic Theoretical Study on Structural, Stability, Electronic, and Spectral Properties of Si2 Mg n Q (Q = 0, ±1; n = 1-11) Clusters of Silicon-Magnesium Sensor Material.

By using CALYPSO searching method and Density Functional Theory (DFT) method at the B3LYP/6-311G (d) level of cluster method, a systematic study of the structures, stabilities, electronic and spectral properties of Si2 Mg n Q (n = 1-11; Q = 0, ±1) clusters of silicon-magnesium sensor material, is performed. According to the calculations, it was found that when n > 4, most stable isomers in Si2 Mg n Q (n = 1-11; Q = 0, ±1) clusters of silicon-magnesium sensor material are three-dimensional structures. Interestingly, although large size Si2 Mg n Q clusters show cage-like structures, silicon atoms are not in the center of the cage, but tend to the edge. The Si2 Mg 1 , 5 , 6 , 8 - 1 and Si2 Mg 13 , 4 , 7 , 9 , 10 + 1 clusters obviously differ to their corresponding neutral structures, which are in good agreement with the calculated values of VIP, AIP, VEA, and AEA. |VIP-VEA| values reveal that the hardness of Si2Mgn clusters decreases with the increase of magnesium atoms. The relative stabilities of neutral and charged Si2 Mg n Q (n = 1-11; Q = 0, ±1) clusters of silicon-magnesium sensor material is analyzed by calculating the average binding energy, fragmentation energy, second-order energy difference and HOMO-LUMO gaps. The results reveal that the Si2 Mg 3 0 , Si2 Mg 3 - 1 , and Si2 Mg 3 + 1 clusters have stronger stabilities than others. NCP and NEC analysis results show that the charges in Si2 Mg n Q (n = 1-11; Q = 0, ±1) clusters of silicon-magnesium sensor material transfer from Mg atoms to Si atoms except for Si2 Mg 1 + 1 , and strong sp hybridizations are presented in Si atoms of Si2 Mg n Q clusters. Finally, the infrared (IR) and Raman spectra of all ground state of Si2 Mg n Q (n = 1-11; Q = 0, ±1) clusters of silicon magnesium sensor material are also discussed.