Patched1-ArhGAP36-PKA-Inversin axis determines the ciliary translocation of Smoothened for Sonic Hedgehog pathway activation.
Animals
Cilia
/ metabolism
Cyclic AMP-Dependent Protein Kinases
/ metabolism
GTPase-Activating Proteins
/ metabolism
HEK293 Cells
Hedgehog Proteins
/ metabolism
Humans
Mice
Patched-1 Receptor
/ metabolism
Phosphorylation
Signal Transduction
Smoothened Receptor
/ metabolism
Transcription Factors
/ metabolism
Inversin
PKA
Patched1
Smoothened
Sonic Hedgehog pathway
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
15 01 2019
15 01 2019
Historique:
pubmed:
2
1
2019
medline:
14
3
2019
entrez:
2
1
2019
Statut:
ppublish
Résumé
The Sonic Hedgehog (Shh) pathway conducts primarily in the primary cilium and plays important roles in cell proliferation, individual development, and tumorigenesis. Shh ligand binding with its ciliary membrane-localized transmembrane receptor Patched1 results in the removal of Patched1 from and the translocation of the transmembrane oncoprotein Smoothened into the cilium, leading to Shh signaling activation. However, how these processes are coupled remains unknown. Here, we show that the Patched1-ArhGAP36-PKA-Inversin axis determines the ciliary translocation of Smoothened. We find that Patched1 interacts with and stabilizes the PKA negative regulator ArhGAP36 to the centrosome. Activating the Shh pathway results in the removal of ArhGAP36 from the mother centriole and the centrosomal PKA accumulation. This PKA then phosphorylates Inversin and promotes its interaction with and the ciliary translocation of Smoothened. Knockdown of
Identifiants
pubmed: 30598432
pii: 1804042116
doi: 10.1073/pnas.1804042116
pmc: PMC6338837
doi:
Substances chimiques
ARHGAP36 protein, human
0
GTPase-Activating Proteins
0
Hedgehog Proteins
0
INVS protein, human
0
Patched-1 Receptor
0
Smoothened Receptor
0
Transcription Factors
0
Cyclic AMP-Dependent Protein Kinases
EC 2.7.11.11
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
874-879Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
Cell. 2013 Jan 17;152(1-2):210-23
pubmed: 23332756
PLoS One. 2009;4(4):e5182
pubmed: 19365551
J Biol Chem. 2009 Jul 31;284(31):20876-84
pubmed: 19366682
J Biol Chem. 2017 Jan 27;292(4):1351-1360
pubmed: 27979967
Proc Natl Acad Sci U S A. 2017 Dec 26;114(52):E11141-E11150
pubmed: 29229834
J Cell Sci. 2010 Jan 1;123(Pt 1):62-9
pubmed: 20016067
Dev Cell. 2016 Aug 22;38(4):333-44
pubmed: 27554855
Genes Dev. 2010 Apr 1;24(7):670-82
pubmed: 20360384
Cell. 2016 Aug 25;166(5):1176-1187.e14
pubmed: 27545348
J Cell Biol. 2009 Nov 2;187(3):365-74
pubmed: 19948480
Nat Med. 2009 Sep;15(9):1055-61
pubmed: 19701205
Hum Mol Genet. 2013 Jan 1;22(1):124-39
pubmed: 23026747
J Biol Chem. 2005 Mar 11;280(10):8800-7
pubmed: 15618230
Differentiation. 2012 Feb;83(2):S49-55
pubmed: 22206729
Sci Signal. 2014 Jul 01;7(332):ra62
pubmed: 24985345
Cancer Cell. 2015 Mar 9;27(3):342-53
pubmed: 25759020
Dev Cell. 2012 Oct 16;23(4):823-35
pubmed: 22981989
Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):17900-7
pubmed: 15598741
Development. 2011 Nov;138(22):4921-30
pubmed: 22007132
Nat Rev Mol Cell Biol. 2013 Jul;14(7):416-29
pubmed: 23719536
Nat Cell Biol. 2017 Apr 27;19(5):493-503
pubmed: 28446817
PLoS Genet. 2015 Aug 20;11(8):e1005473
pubmed: 26291458
PLoS Biol. 2016 Jun 09;14(6):e1002481
pubmed: 27280464
J Cell Biol. 2010 Oct 18;191(2):415-28
pubmed: 20956384
BMC Biol. 2011 Feb 28;9:14
pubmed: 21356043
Nat Genet. 2003 Aug;34(4):413-20
pubmed: 12872123
Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):11061-6
pubmed: 25024229
Nat Commun. 2016 Oct 07;7:12963
pubmed: 27713425
Genes Dev. 2002 Nov 1;16(21):2743-8
pubmed: 12414725
Nat Genet. 1998 Oct;20(2):149-56
pubmed: 9771707
J Cell Biol. 2016 Mar 28;212(7):861-75
pubmed: 27002170
Nature. 1998 Jan 1;391(6662):90-2
pubmed: 9422511
J Cell Sci. 2009 Jan 1;122(Pt 1):44-54
pubmed: 19050042
Nat Chem Biol. 2015 Apr;11(4):246-55
pubmed: 25785427
J Cell Biol. 2010 Jan 11;188(1):21-8
pubmed: 20048263
PLoS Biol. 2015 Apr 10;13(4):e1002129
pubmed: 25860027
Nature. 2007 Nov 8;450(7167):252-8
pubmed: 17960137
Nat Cell Biol. 2005 Jan;7(1):86-92
pubmed: 15592457
Elife. 2016 Oct 05;5:
pubmed: 27705744
Nat Rev Clin Oncol. 2015 Aug;12(8):445-64
pubmed: 25850553
Science. 2007 Jul 20;317(5836):372-6
pubmed: 17641202
Nature. 2005 Oct 13;437(7061):1018-21
pubmed: 16136078
Nat Commun. 2014 Oct 07;5:5034
pubmed: 25289679
Cancer Res. 2006 Oct 15;66(20):10171-8
pubmed: 17047082
Cell Res. 2013 Feb;23(2):186-200
pubmed: 23337587
Cell. 2018 Sep 20;175(1):295-297
pubmed: 30241610
Mol Cell. 2017 Apr 6;66(1):154-162.e10
pubmed: 28344083
Development. 2014 Sep;141(17):3331-9
pubmed: 25085974
Dev Cell. 2015 Nov 23;35(4):497-512
pubmed: 26585297
PLoS Biol. 2011 Jun;9(6):e1001083
pubmed: 21695114
Nature. 2004 Dec 23;432(7020):1045-50
pubmed: 15616566
Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7786-91
pubmed: 27357676
Nat Genet. 2005 May;37(5):537-43
pubmed: 15852005