Mouse Rab23 regulates Hedgehog signaling from Smoothened to Gli proteins Journal Article


Authors: Eggenschwiler, J. T.; Bulgakov, O. V.; Qin, J.; Li, T.; Anderson, K. V.
Article Title: Mouse Rab23 regulates Hedgehog signaling from Smoothened to Gli proteins
Abstract: 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. © 2005 Elsevier Inc. All rights reserved.
Keywords: immunohistochemistry; signal transduction; controlled study; carrier protein; unclassified drug; mutation; nonhuman; protein analysis; mouse; animals; mice; sonic hedgehog protein; animal experiment; hedgehog proteins; mice, mutant strains; nerve tissue proteins; transcription factor; neurons; immunofluorescence; animalia; vertebrata; in situ hybridization; transcription factor gli2; spinal cord; membrane protein; kruppel-like transcription factors; pregnancy; trans-activators; sonic hedgehog; erinaceidae; receptors, g-protein-coupled; transcription factor gli1; transcription factor gli3; body patterning; neural tube; gli2; smoothened; receptors, cell surface; patterning; cyclic amp-dependent protein kinases; protein patched; gli3; rab23; protein rab23; protein smoothened; rab gtp-binding proteins
Journal Title: Developmental Biology
Volume: 290
Issue: 1
ISSN: 0012-1606
Publisher: Elsevier Inc.  
Date Published: 2006-02-01
Start Page: 1
End Page: 12
Language: English
DOI: 10.1016/j.ydbio.2005.09.022
PUBMED: 16364285
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 61" - "Export Date: 4 June 2012" - "CODEN: DEBIA" - "Source: Scopus"
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  1. Kathryn Anderson
    148 Anderson