Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli

Scott R May; Amir M Ashique; Mattias Karlen; Baolin Wang; Yiguo Shen; Kostantinos Zarbalis; Jeremy Reiter; Johan Ericson; Andrew S Peterson

doi:10.1016/j.ydbio.2005.08.050

Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli

Dev Biol. 2005 Nov 15;287(2):378-89. doi: 10.1016/j.ydbio.2005.08.050. Epub 2005 Oct 17.

Authors

Scott R May¹, Amir M Ashique, Mattias Karlen, Baolin Wang, Yiguo Shen, Kostantinos Zarbalis, Jeremy Reiter, Johan Ericson, Andrew S Peterson

Affiliation

¹ Ernest Gallo Clinic and Research Center, Emeryville, CA 94608, USA.

PMID: 16229832
DOI: 10.1016/j.ydbio.2005.08.050

Abstract

Sonic Hedgehog (Shh) signals are transduced into nuclear ratios of Gli transcriptional activator versus repressor. The initial part of this process is accomplished by Shh acting through Patched (Ptc) to regulate Smoothened (Smo) activity. The mechanisms by which Ptc regulates Smo, and Smo activity is transduced to processing of Gli proteins remain unclear. Recently, a forward genetic approach in mice identified a role for intraflagellar transport (IFT) genes in Shh signal transduction, downstream of Patched (Ptc) and Rab23. Here, we show that the retrograde motor for IFT is required in the mouse for the phenotypic expression of both Gli activator and repressor function and for effective proteolytic processing of Gli3. Furthermore, we show that the localization of Smo to primary cilia is disrupted in mutants. These data indicate that primary cilia act as specialized signal transduction organelles required for coupling Smo activity to the biochemical processing of Gli3 protein.

MeSH terms

Amino Acid Sequence
Animals
Body Patterning
Cilia / metabolism*
Cilia / ultrastructure
Dyneins / genetics
Dyneins / metabolism*
Extremities / embryology
Flagella / metabolism
Gene Expression Regulation, Developmental
Hedgehog Proteins
Kruppel-Like Transcription Factors / metabolism
Kruppel-Like Transcription Factors / physiology*
Mice
Microscopy, Electron, Scanning
Molecular Motor Proteins / genetics
Molecular Motor Proteins / metabolism*
Molecular Sequence Data
Mutation
Nerve Tissue Proteins / metabolism
Nerve Tissue Proteins / physiology*
Prosencephalon / abnormalities
Prosencephalon / embryology
Protein Transport / genetics
Receptors, G-Protein-Coupled / metabolism*
Smoothened Receptor
Spinal Cord / abnormalities
Spinal Cord / embryology
Trans-Activators / physiology
Zinc Finger Protein Gli3

Substances

Gli3 protein, mouse
Hedgehog Proteins
Kruppel-Like Transcription Factors
Molecular Motor Proteins
Nerve Tissue Proteins
Receptors, G-Protein-Coupled
Shh protein, mouse
Smo protein, mouse
Smoothened Receptor
Trans-Activators
Zinc Finger Protein Gli3
Dnchc2 protein, mouse
Dyneins