Disease relevance of Rab23

• Rab23 is the product of the gene mutated in the mouse open brain1 phenotype, which displays neural tube defects [1].

High impact information on Rab23

• The data indicate that dorsalizing signals activate transcription of Rab23 in order to silence the Shh pathway in dorsal neural cells [2].
• We cloned opb by a map-based approach and found that it encodes Rab23, a member of the Rab family of vesicle transport proteins [2].
• Analysis of Gli3 protein suggests that Rab23 also has a role in promoting the production of Gli3 repressor [3].
• Mouse Rab23 regulates hedgehog signaling from smoothened to Gli proteins [3].
• Genetic analyses have now shown that Rab23 functions downstream of Smo and affects the function of the Shh-regulated Gli family of transcription factors in a more direct manner than previously thought [1].

Biological context of Rab23

• We have examined the expression pattern of the putative antagonists Rab23 and Slimb/betaTrCP during early murine odontogenesis and find that these molecules are expressed in the developing tooth [4].
• Expression of Rab23 in the adult brain is suggestive, however, of having a postnatal function beyond its role in embryonic development [5].

Anatomical context of Rab23

• Here, we demonstrate that Rab23 acts upstream of Gli transcription factors in patterning neural cell types in the spinal cord [3].
• Interestingly, Rab23 demonstrates contrasting expression domains in the incisor and molar dentition during the cap stage, being restricted to the mesenchymal compartment of molar teeth and the epithelium of the enamel knot in incisor teeth [4].
• 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 [5].
• 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 [5].
• Rab23 is found in the cytosol as well as being associated with the plasma and endosomal membranes [5].

Regulatory relationships of Rab23

• Because the phenotypes of Rab23 mutations in mice and humans include defects in cartilage and bone development, our study suggests that Rab23 is involved in the control of Sox9 expression via Gli1 protein [6].

Other interactions of Rab23

• For example, the vesicle transport protein Rab23 is a cell autonomous negative regulator of Shh signaling, but the process affected by Rab23 has not been defined [3].
• Expression of the Hedgehog antagonists Rab23 and Slimb/betaTrCP during mouse tooth development [4].
• 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 [5].
• A Northern analysis revealed that the rab23 mRNA is predominantly expressed in the brain, which places the protein, together with Rab3a and Rab15, in the group of small GTPases characteristic of the nervous system [7].

Analytical, diagnostic and therapeutic context of Rab23

• The full-length cDNA encoding Rab23, a novel Ras-related small GTPase, was isolated using the sequence of a previously described [Chavrier et al., Gene 112 (1992) 261-264] short cDNA fragment and the rapid amplification of cDNA ends (RACE) PCR techniques [7].
• We describe the methods used to design and make the Rab23 expression constructs, and to assess their localization relative to key hedgehog pathways and endocytic markers in both transiently and stably transfected cell cultures [8].

References