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Ee Ling Ng

Publications and source records attributed to Ee Ling Ng.

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

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.

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Rab23: what exactly does it traffic?

Rab23 is the product of the gene mutated in the mouse open brain1 phenotype, which displays neural tube defects. It appears to antagonize sonic hedgehog (Shh)-mediated signaling during mouse development, presumably by regulating the intracellular trafficking of one or more of Shh's-signaling components. The Shh receptor Patched1 (Ptch1) and its downstream effector Smoothened (Smo) were initial prime suspects as they are membrane proteins whose cellular dynamics are modulated by the Shh signal. However, Rab23 mutants do not appear to affect the localization and dynamics of either protein. 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. A plethora of proteins that influence Shh signaling and whose cellular trafficking could potentially be regulated by Rab23 has also emerged. These include members of the intraflagellar transport complex, as well as motor proteins responsible for their assembly at the cilia. Rab23 is also expressed in adult mouse neurons and may thus have functions beyond embryonic developmental stages and Shh signaling. We discuss these new findings and explore the myriad of possibilities whereby Rab23 may function.

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