Mouse Rab23 regulates hedgehog signaling from smoothened to Gli proteins.
Sonic hedgehog (Shh) signaling is required for the growth and patterning of many tissues in vertebrate embryos, but important aspects of the Shh signal transduction pathway are poorly understood. 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. Here, we demonstrate that Rab23 acts upstream of Gli transcription factors in patterning neural cell types in the spinal cord. Double mutant analysis indicates that the primary target of Rab23 is the Gli2 activator and that Rab23 and Gli3 repressor have additive effects on patterning. Analysis of Gli3 protein suggests that Rab23 also has a role in promoting the production of Gli3 repressor. Although the membrane proteins Patched and Smoothened change subcellular localization in response to Shh, double mutant analysis demonstrates that Rab23 does not work through either Patched or Smoothened. Instead, Rab23 appears to regulate subcellular localization of essential components of the Hedgehog pathway that act downstream of Smoothened and upstream of Gli proteins.
Eggenschwiler
Jonathan T
JT
Developmental Biology Program, Sloan Kettering Institute, New York, NY 10021, USA.
Bulgakov
Oleg V
OV
Qin
Jian
J
Li
Tiansen
T
Anderson
Kathryn V
KV
D000818:Animals; D019521:Body Patterning; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D000072079:Patched Receptors; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
C000618551:Gli2 protein, mouse; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D015534:Trans-Activators; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3; D017868:Cyclic AMP-Dependent Protein Kinases; C431746:Rab23 protein, mouse; D020691:rab GTP-Binding Proteins