PMID- 20956384
OWN - NLM
STAT- MEDLINE
DCOM- 20110222
LR  - 20220309
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 191
IP  - 2
DP  - 2010 Oct 18
TI  - A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and 
      dissociation of SuFu-Gli protein complexes.
PG  - 415-28
LID - 10.1083/jcb.201004108 [doi]
AB  - In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the 
      membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the 
      transcriptional effectors of the pathway. In the absence of signaling, Gli 
      proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It 
      is unclear how Hh activates Gli and whether it directly regulates SuFu. We find 
      that Hh stimulation quickly recruits endogenous SuFu-Gli complexes to cilia, 
      suggesting a model in which Smo activates Gli by relieving inhibition by SuFu. In 
      support of this model, we find that Hh causes rapid dissociation of the SuFu-Gli 
      complex, thus allowing Gli to enter the nucleus and activate transcription. 
      Activation of protein kinase A (PKA), an inhibitor of Hh signaling, blocks 
      ciliary localization of SuFu-Gli complexes, which in turn prevents their 
      dissociation by signaling. Our results support a simple mechanism in which Hh 
      signals at vertebrate cilia cause dissociation of inactive SuFu-Gli complexes, a 
      process inhibited by PKA.
FAU - Tukachinsky, Hanna
AU  - Tukachinsky H
AD  - Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
FAU - Lopez, Lyle V
AU  - Lopez LV
FAU - Salic, Adrian
AU  - Salic A
LA  - eng
GR  - R01 GM092924/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Gli1 protein, mouse)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Repressor Proteins)
RN  - 0 (Smo protein, mouse)
RN  - 0 (Smoothened Receptor)
RN  - 0 (Sufu protein, mouse)
RN  - 0 (Zinc Finger Protein GLI1)
SB  - IM
MH  - Animals
MH  - Cilia/*metabolism
MH  - Enzyme Activation
MH  - Hedgehog Proteins/genetics/*metabolism
MH  - Kruppel-Like Transcription Factors/analysis/genetics/*metabolism
MH  - Mice
MH  - Microtubules/metabolism
MH  - Models, Genetic
MH  - NIH 3T3 Cells
MH  - Protein Biosynthesis
MH  - Protein Transport
MH  - Receptors, G-Protein-Coupled/genetics/metabolism/physiology
MH  - Repressor Proteins/analysis/genetics/*metabolism
MH  - *Signal Transduction
MH  - Smoothened Receptor
MH  - Zinc Finger Protein GLI1
PMC - PMC2958481
EDAT- 2010/10/20 06:00
MHDA- 2011/02/23 06:00
PMCR- 2011/04/18
CRDT- 2010/10/20 06:00
PHST- 2010/10/20 06:00 [entrez]
PHST- 2010/10/20 06:00 [pubmed]
PHST- 2011/02/23 06:00 [medline]
PHST- 2011/04/18 00:00 [pmc-release]
AID - jcb.201004108 [pii]
AID - 201004108 [pii]
AID - 10.1083/jcb.201004108 [doi]
PST - ppublish
SO  - J Cell Biol. 2010 Oct 18;191(2):415-28. doi: 10.1083/jcb.201004108.