Interaction of smoothened with integrin-linked kinase in primary cilia mediates Hedgehog signalling

被引：25

作者：

Barakat, Badia ^{[1
]}

Yu, Liang ^{[1
]}

Lo, Camden ^{[2
,3
]}

Duc Vu ^{[1
]}

De Luca, Elisabetta ^{[1
]}

Cain, Jason E. ^{[1
]}

Martellotto, Luciano G. ^{[1
]}

Dedhar, Shoukat ^{[4
,5
]}

Sadler, Anthony J. ^{[1
]}

Wang, Die ^{[1
]}

Watkins, D. Neil ^{[1
]}

Hannigan, Gregory E. ^{[1
]}

机构：

[1] Monash Univ, Ctr Canc Res, Clayton, Vic 3168, Australia

[2] Monash Univ, Monash Micro Imaging, Clayton, Vic 3168, Australia

[3] Monash Inst Med Res, Clayton, Vic 3168, Australia

[4] Univ British Columbia, BC Canc Agcy, Vancouver, BC V5Z 1M9, Canada

[5] Univ British Columbia, Dept Biochem, Vancouver, BC, Canada

来源：

EMBO REPORTS | 2013年 / 14卷 / 09期

基金：

英国医学研究理事会; 加拿大健康研究院;

关键词：

cerebellar development; Hedgehog signalling; integrin-linked kinase; primary cilium; CELL LINEAGE; EXPRESSION; PROLIFERATION; VISUALIZATION; LOCALIZATION; CILIOGENESIS; REVEALS; PATTERN; PARVIN; GENES;

D O I：

10.1038/embor.2013.110

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Here we report that ILK localizes in the mouse primary cilium, a sensory organelle required for signalling by the Hedgehog (Hh) pathway. Genetic or pharmacological inhibition of ILK blocks ciliary accumulation of the Hh pathway effector smoothened (Smo) and suppresses the induction of Gli transcription factor mRNAs by SHh. Conditional deletion of ILK or Smo also inhibits SHh-driven activation of Gli2 in the embryonic mouse cerebellum. ILK regulation of Hh signalling probably requires the physical interaction of ILK and Smo in the cilium, and we also show selective cilia-associated interaction of ILK with beta-arrestin, a known mediator of Smo-dependent signalling.

引用

页码：837 / 844

页数：8

共 40 条

[1] Small molecule modulation of Smoothened activity [J].

Chen, JK ;

Taipale, J ;

Young, KE ;

Maiti, T ;

Beachy, PA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (22) :14071-14076

[2] Sonic Hedgehog Dependent Phosphorylation by CK1α and GRK2 Is Required for Ciliary Accumulation and Activation of Smoothened [J].

Chen, Yongbin ;

Sasai, Noriaki ;

Ma, Guoqiang ;

Yue, Tao ;

Jia, Jianhang ;

Briscoe, James ;

Jiang, Jin .

PLOS BIOLOGY, 2011, 9 (06)

[3] The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation [J].

Clement, Christian A. ;

Kristensen, Stine G. ;

Mollgard, Kjeld ;

Pazour, Gregory J. ;

Yoder, Bradley K. ;

Larsen, Lars A. ;

Christensen, Soren T. .

JOURNAL OF CELL SCIENCE, 2009, 122 (17) :3070-3082

[4] Vertebrate Smoothened functions at the primary cilium [J].

Corbit, KC ;

Aanstad, P ;

Singla, V ;

Norman, AR ;

Stainier, DYR ;

Reiter, JF .

NATURE, 2005, 437 (7061) :1018-1021

[5] The level of sonic hedgehog signaling regulates the complexity of cerebellar foliation [J].

Corrales, JD ;

Blaess, S ;

Mahoney, EM ;

Joyner, AL .

DEVELOPMENT, 2006, 133 (09) :1811-1821

[6] Spatial pattern of sonic hedgehog signaling through Gli genes during cerebellum development [J].

Corrales, JMD ;

Rocco, GL ;

Blaess, S ;

Guo, QX ;

Joyner, AL .

DEVELOPMENT, 2004, 131 (22) :5581-5590

[7] Pattern formation in the vertebrate neural tube: a sonic hedgehog morphogen-regulated transcriptional network [J].

Dessaud, Eric ;

McMahon, Andrew P. ;

Briscoe, James .

DEVELOPMENT, 2008, 135 (15) :2489-2503

[8] Induction of Ran GTP drives ciliogenesis [J].

Fan, Shuling ;

Whiteman, Eileen L. ;

Hurd, Toby W. ;

McIntyre, Jeremy C. ;

Dishinger, John F. ;

Liu, Chia Jen ;

Martens, Jeffrey R. ;

Verhey, Kristen J. ;

Sajjan, Uma ;

Margolis, Ben .

MOLECULAR BIOLOGY OF THE CELL, 2011, 22 (23) :4539-4548

[9] Proper cerebellar development requires expression of β1-integrin in Bergmann glia, but not in granule neurons [J].

Frick, Alexandra ;

Grammel, Daniel ;

Schmidt, Felix ;

Poeschl, Julia ;

Priller, Markus ;

Pagella, Pierfrancesco ;

Von Bueren, Andre O. ;

Peraud, Aurelia ;

Tonn, Joerg-Christian ;

Herms, Jochen ;

Rutkowski, Stefan ;

Kretzschmar, Hans A. ;

Schueller, Ulrich .

GLIA, 2012, 60 (05) :820-832

[10] The Pseudoactive Site of ILK Is Essential for Its Binding to α-Parvin and Localization to Focal Adhesions [J].

Fukuda, Koichi ;

Gupta, Sudhiranjan ;

Chen, Ka ;

Wu, Chuanyue ;

Qin, Jun .

MOLECULAR CELL, 2009, 36 (05) :819-830

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