TMEM203 Activators

TMEM203 activators can be broadly classified into two categories: those that directly affect intracellular calcium levels and those that influence signaling pathways to achieve similar effects. For instance, Ionomycin is a calcium ionophore that allows calcium to flood into the cell, thereby necessitating the activation of TMEM203 to maintain balanced ER calcium levels. Similarly, Fura-2/AM acts as a calcium indicator but has the added ability to increase cytosolic calcium concentrations, making it a de facto activator of TMEM203 for ER calcium regulation.

In the second category are compounds that modulate specific signaling pathways which indirectly cause TMEM203 activation. For example, PMA activates Protein Kinase C (PKC), which has downstream effects on ER calcium levels, thus triggering TMEM203 for calcium reuptake into the ER. Another example is Calcitriol, the active form of vitamin D3, which promotes intestinal calcium absorption. Increased calcium in the system necessitates cellular adjustments in calcium storage, hence activating TMEM203 to regulate calcium levels within the ER. Both categories serve the core function of activating TMEM203 to regulate intracellular calcium homeostasis, albeit via different mechanisms.