Stability and association of Smoothened, Costal2 and Fused with Cubitus interruptus are regulated by Hedgehog

Laurent Ruel; Ralph Rodriguez; Armel Gallet; Laurence Lavenant-Staccini; Pascal P Thérond

doi:10.1038/ncb1052

Stability and association of Smoothened, Costal2 and Fused with Cubitus interruptus are regulated by Hedgehog

Nat Cell Biol. 2003 Oct;5(10):907-13. doi: 10.1038/ncb1052. Epub 2003 Oct 1.

Authors

Laurent Ruel¹, Ralph Rodriguez, Armel Gallet, Laurence Lavenant-Staccini, Pascal P Thérond

Affiliation

¹ Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre de Biochimie, Parc Valrose, 06108 Nice Cedex 02, France.

PMID: 14523402
DOI: 10.1038/ncb1052

Abstract

The mechanisms involved in transduction of the Hedgehog (Hh) signal are of considerable interest to developmental and cancer biologists. Stabilization of the integral membrane protein Smoothened (Smo) at the plasma membrane is a crucial step in Hh signalling but the molecular events immediately downstream of Smo remain to be elucidated. We have shown previously that the transcriptional mediator Cubitus interruptus (Ci) is associated in a protein complex with at least two other proteins, the kinesin-like Costal2 (Cos2) and the serine-threonine kinase Fused (Fu). This protein complex governs the access of Ci to the nucleus. Here we show that, consequent on the stabilization of Smo, Cos2 and Fu are destabilized. Moreover, we find that the Cos2-Fu-Ci protein complex is associated with Smo in membrane fractions both in vitro and in vivo. We also show that Cos2 binding on Smo is necessary for the Hh-dependent dissociation of Ci from this complex. We propose that the association of the Cos2 protein complex with Smo at the plasma membrane controls the stability of the complex and allows Ci activation, eliciting its nuclear translocation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Active Transport, Cell Nucleus / physiology
Animals
Cell Membrane / metabolism
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Drosophila Proteins / genetics
Drosophila Proteins / metabolism*
Drosophila melanogaster / embryology
Drosophila melanogaster / physiology
Embryonic Structures / cytology
Embryonic Structures / metabolism
Gene Expression Regulation, Developmental
Hedgehog Proteins
Kinesins / genetics
Kinesins / metabolism*
Macromolecular Substances
Protein Binding
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
Receptors, G-Protein-Coupled / genetics
Receptors, G-Protein-Coupled / metabolism*
Signal Transduction / physiology
Smoothened Receptor
Transcription Factors
Transport Vesicles / metabolism

Substances

DNA-Binding Proteins
Drosophila Proteins
Hedgehog Proteins
Macromolecular Substances
Receptors, G-Protein-Coupled
Smoothened Receptor
Transcription Factors
ci protein, Drosophila
cos protein, Drosophila
smo protein, Drosophila
hh protein, Drosophila
fu protein, Drosophila
Protein Serine-Threonine Kinases
Kinesins