Figure 8.

Proposed model for the role of TRPC1 in Darier's disease: We propose that in Darier's disease keratinocytes, the nonfunctional SERCA fails to maintain the adequate ER calcium pool (⊝, compromised function). This decreased SERCA activity in turn up-regulates the store-operated plasma membrane calcium channel TRPC1, in an undefined mechanism dependent on NF-κB. Overexpressed TRPC1 channels augment store-operated calcium influx. The incoming calcium is pumped out via the plasma membrane calcium ATPase (PMCA) and also used for the cells physiological need. An optimal level of this calcium brings about proper growth and proliferation (⊕, positive effect) by activating NF-κB pathway. This confers resistance to apoptosis by regulating the expression of proproliferative/antiapoptotic genes. However, if there is an overload this calcium might be detrimental, leading to stress-induced apoptosis or uncontrolled proliferation accounting for cancerous state (?). It is also proposed that isotretinoin, by yet another undefined mechanism (?) regulates the calcium influx via TRPC1 and blocks the calcium overload, thereby inhibiting hyperproliferation and probably cancer.