Age-associated decline in RAB-10 efficacy impairs intestinal barrier integrity

We conducted a comprehensive examination of the mechanism responsible for the dysfunction of adherens junctions due to aging. A previous study has demonstrated that RAB-10-mediated endocytic recycling is essential for adherens junction assembly (Liu et al., 2018). Our study corroborated this association and revealed that SDPN-1/PACSINs is upregulated in aged animals, and that dimeric SDPN-1 inhibits RAB-10 activation by competing with the DENN-4/GEF for binding to inactive RAB-10(GDP) during endocytic recycling, which contributes to the deterioration of adherens junctions with age. Furthermore, the age-related activity relief of KGB-1/JUN kinase is indispensable for SDPN-1's efficacy.