Open brain gene product Rab23: Expression pattern in the adult mouse brain and functional characterization

Abstract

The gene mutated in the mouse open brain (opb) phenotype antagonizes sonic hedgehog-mediated signaling and encodes a small GTPase of the Rab family, Rab23. To date, the brain expression profile and exact mechanism of function of the Rab23 protein has remained unknown. Specific antibodies generated against Rab23 showed that the protein is highly enriched in the adult rodent brain and present in low levels in multiple tissues of the adult rodent. Rab23 is found in the cytosol as well as being associated with the plasma and endosomal membranes. In the adult mouse brain, Rab23 is found in betaIII tubulin (TuJ) positive neuronal cell bodies and are most prominent in the cortex, hypothalamus and the cerebellum. It is, however, absent from glial fibrillary acidic protein (GFAP) positive astrocytes or CNPase positive oligodendrocytes. Despite the plasma membrane/endosomal membrane localization of Rab23, neither overexpression of the GTP-restricted nor the GDP-bound mutant forms affect internalization of transferrin or epidermal growth factor. Exogenous overexpression of Rab23 or its mutants also did not affect the morphological differentiation of thalamic neurons in culture. Expression of Rab23 in the adult brain is suggestive, however, of having a postnatal function beyond its role in embryonic development.

A novel role for Rab23 in the trafficking of Kif17 to the primary cilium

“…Immunostaining with anti-Rab23 antibodies (Guo et al, 2006) has shown that endogenous Rab23 is generally cytosolic and associated with subcellular membranous structures, but that its localization at the primary cilia cannot be easily discerned. To test whether overexpression of Rab23 could demonstrate clearer cilia localization, cells expressing wild-type Rab23, GTPaseactivity-deficient Rab23 Q68L (constitutively active), GTP-bindingdefective Rab23 S23N (dominant negative) and the nonphosphorylatable Rab23 T150A mutants (hereafter denoted Rab23WT, Rab23QL, Rab23SN and Rab23TA, respectively) were compared.…”

“…Based on the strong association of Rab23 with the primary cilium, its high levels of expression in neurons (Guo et al, 2006), and the involvement of Rab23 in Kif17 ciliary trafficking, Rab23 could be required in the transport of the known cargoes of the motor protein, which are, together, essential for various neuronal functions. Beyond the neuronal context, the role of the ciliary transport of Rab23 could also extend across various cell types, such as fibroblasts and epithelial cells.…”

“…The widespread distribution of Rab23 across metazoans suggests that there is a fundamental physiological role of Rab23 beyond Shh signaling (Guo et al, 2006;Lumb and Field, 2011). In addition, high Rab23 expression levels in adult mouse brains hinted at a postnatal function beyond embryogenesis.…”

Drosophila Rab23 Is Involved in the Regulation of the Number and Planar Polarization of the Adult Cuticular Hairs

“…However, in the case of the abdominal cuticle, Hh overexpression induces reversed hair polarity (Struhl et al 1997;Lawrence et al 1999), that is clearly distinct from the effect of Rab23, which induces randomized polarity and multiple hairs ( Figure 3). Together, these findings indicate that although the Rab23 protein appears to be highly conserved throughout evolution (Guo et al 2006), its role in Hh signaling is likely to be restricted only to vertebrates.…”

Thirty-One Flavors of Drosophila Rab Proteins

“…These results suggest that Rab proteins modulate Smo localization by regulating endocytosis and perhaps also exocytosis. Mouse Rab23 is a negative regulator of Hh signaling in the developing neural tube (Eggenschwiler et al 2001(Eggenschwiler et al , 2006Evans et al 2003Evans et al , 2005Guo et al 2006;Wang et al 2006). These studies clearly indicate that Rab proteins are important for controlling developmental signals to ensure proper morphogenesis and organismal growth.…”