Nervous systems within bilateral organisms display a remarkable degree of left-right symmetry. However, notable instances of left-right neuronal asymmetry have been evolutionarily conserved and are established by mechanisms that are not fully understood. The C. elegans AWC olfactory neuron pair undergoes a stochastic decision during late embryogenesis to differentiate asymmetrically into two subtypes, default AWCOFF and induced AWCON. Intercellular calcium signaling between the two AWC and non-AWC cells within a NSY-5 gap junction network coordinates AWC asymmetry. The innexin gap junction protein NSY-5 and the claudin adhesion protein NSY-4 act in parallel to suppress UNC-2/UNC-36 and EGL-19/UNC-36 calcium channel-mediated signaling by activating both SLO-1 and SLO-2 BK potassium channels to promote AWCON. However, it is unknown how
slo-1 and
slo-2 function to specify AWCON. To identify the molecular mechanisms by which
slo-1 and
slo-2 promote AWCON, we performed a forward genetic suppressor screen with
slo-1 gain-of-function (2AWCON) mutants and identified several downstream genes of
slo-1 called mok genes (modifier of K+ channels). Among these, the
mok-2(
vy149) missense mutation exhibits a 2AWCOFF phenotype, indicating that it has a role in inducing the AWCON subtype. Whole genome sequencing revealed that
mok-2 encodes a claudin-like protein with four transmembrane domains that is typically associated with tight junction complexes. We generated a
mok-2 null allele using CRISPR/Cas9, and showed that it also displays a 2AWCOFF phenotype, further supporting the essential role of
mok-2 in promoting AWCON. In addition, our genetic studies suggest that
mok-2 functions in a cell autonomous manner downstream of
slo-1 to inhibit the calcium channel-mediated signaling to promote the AWCON subtype. Furthermore, translational GFP reporters under the control of an AWC-specific promoter revealed that while MOK-2 is predominantly localized to the AWC dendritic tip region, the MOK-2
(vy149) mutant fails to be trafficked towards the dendritic tip and accumulates in the cell body, resulting in a heterogeneous distribution pattern. Based on its putative subcellular localization and claudin-like structure, these data suggest that
mok-2 may communicate with other cells in the ciliary region to have non-cell autonomous roles in the AWCON/AWCOFF asymmetric subtype decision. Our preliminary data using translational mNeonGreen reporter strains generated with CRISPR/Cas9 show that
mok-2 may be expressed in supporting cells, such as glial cells in the head. Our study will provide novel insight into how tight junction proteins mediate interactions between sensory neurons and supporting cells to generate sensory neuron diversity.