Regulation of L-type Voltage Gated Calcium Channel CACNA1S in Macrophages upon Mycobacterium tuberculosis Infection
Fig 10
Proposed model for CACNA1S expression by M. tb.
Stimulation of macrophages by M. tb or Rv2463 increases CREB phosphorylation in a TLR dependent MyD88 independent pathway that involves IRAK1 and TRAF6. Phosphorylated CREB (p-CREB) translocates to the nucleus and binds to CACNA1S promoter to induce CACNA1S protein expression. In parallel mycobacterial stimulation attenuates the generation of reactive oxygen species (ROS) that further contributes to CREB phosphorylation. Calcium homeostasis sensors STIM1 and STIM2 also play an inhibitory role in CACNA1S upregulation upon M. tb infection or Rv2463 stimulation.