Optogenetic silencing by combining a rhodopsin cyclase with an engineered cGMP-gated potassium channel.

ABSTRACT: Since the advent of optogenetics, great progress has been made in developing tools to modulate and detect cellular activity using light. We present a two-component optogenetic silencing tool, RoCK (rhodopsin cyclase/K⁺ channel), which pairs the rhodopsin-guanylyl cyclase CaRhGC with customized SthK K⁺ channels that are engineered to open selectively upon guanosine 3',5'-monophosphate (cGMP) binding. By enhancing the cGMP sensitivity and open probability of SthK mutants, we obtained four channel variants suited for different levels of cGMP concentration. CaRhGC's membrane-bound nature enables localized cGMP production, and the lack of dark activity reduces the risk for off-target effects. Optimized RoCK effectively modulated cellular activity in mouse hippocampal neuro

SUBMITTER: Spreen A 

PROVIDER: S-EPMC12662207 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature