Transient receptor potential cation channel subfamily M member 1 (TRPM1) (TRPM1)

Transient receptor potential cation channel subfamily M member 1 (TRPM1) is a non-selective cation channel that plays a fundamental role in the mammalian visual system (UniProt, 2023). It is the primary effector channel in retinal ON-bipolar cells, where it is coupled to the metabotropic glutamate receptor 6 (mGluR6) signaling cascade (Morgans et al., 2009). In the dark, glutamate released by photoreceptors binds to mGluR6, keeping TRPM1 channels closed; light reduces glutamate release, leading to the opening of TRPM1 and subsequent cell depolarization. Mutations in TRPM1 are a major cause of complete congenital stationary night blindness (cCSNB), a condition where the retina fails to transmit signals from photoreceptors to the inner retina (van Genderen et al., 2009). In the context of optogenetics, TRPM1 is a key target for vision restoration therapies aimed at bypassing lost photoreceptors in diseases like retinitis pigmentosa (Cehajic-Kapetanovic et al., 2015). These strategies involve using viral vectors to express light-sensitive proteins that can either directly activate TRPM1 or act as a light-gated version of the channel itself within surviving retinal neurons. By re-establishing light-sensitive cation influx in the ON-pathway, these therapies aim to restore functional visual signals to the brain. Additionally, TRPM1 serves as a diagnostic biomarker in oncology, as its expression is frequently downregulated during the progression of malignant melanoma (Duncan et al., 1998).

Other names

Melastatin-1MLSN1CSNB1CLSNB1Transient receptor potential melastatin 1Opto-TRPM1

The mechanism involves the restoration of light-sensitive cation conductance in retinal ON-bipolar cells. In gene therapy for CSNB, wild-type TRPM1 is delivered to restore the endogenous mGluR6 signaling pathway (van Genderen et al., 2009). In optogenetic applications, engineered light-gated channels or chimeric proteins (e.g., Opto-mGluR6) are expressed to trigger TRPM1-mediated depolarization or mimic its function in response to light, thereby bypassing dysfunctional photoreceptors and restoring visual signaling (Cehajic-Kapetanovic et al., 2015).