Distribution analysis of RAB11A and RAB11B, small GTP-binding proteins, in mice.

Abstract

Background: RAB11 is a small GTP-binding protein that regulates intracellular trafficking of recycling endosomes and is thereby involved in several neural functions. Highly similar RAB11 isoforms are encoded by RAB11A and RAB11B genes, and their pathogenic variants are associated with similar neurodevelopmental disorders, suggesting that RAB11A and RAB11B play similar and important roles in brain development. However, the detailed distribution patterns of these isoforms in various organs, including the brain, remain undetermined.

Methods and results: We generated an antibody against RAB11A and analyzed the distribution of RAB11A and RAB11B in mice. RAB11A was highly expressed in the ovary and the uterus but less abundant in the brain, whereas RAB11B was abundant in the brain, the testis, the ovary, and the uterus. In the developing cortex, RAB11A was enriched in the apical endfeet of apical radial glial cells, whereas RAB11B was abundantly expressed in postmigratory neurons of the cortical plate. In the adult mouse brain, RAB11A and RAB11B were similarly expressed in most neurons, with weak RAB11A signals also observed in the neuropil. In cultured neurons, RAB11A and RAB11B showed only partial co-localization and differential distribution in both soma and neurites. Notably, RAB11A appeared to be more abundant at presynapses than RAB11B.

Conclusions: RAB11A and RAB11B exhibit distinct and characteristic distributions in the brain and other organs, suggesting they play different roles throughout the body. In particular, our results suggest they make distinct contributions to cortical development and regulation of the synaptic vesicle cycle.