scholarly journals Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors

Development ◽  
2005 ◽  
Vol 132 (13) ◽  
pp. 3103-3111 ◽  
Author(s):  
A. Liu
Author(s):  
Yang Yue ◽  
Martin F. Engelke ◽  
T. Lynne Blasius ◽  
Kristen J. Verhey

The kinesin-4 motor KIF7 is a conserved regulator of the Hedgehog signaling pathway. In vertebrates, Hedgehog signaling requires the primary cilium, and KIF7 and Gli transcription factors accumulate at the cilium tip in response to Hedgehog activation. Unlike conventional kinesins, KIF7 is an immotile kinesin and its mechanism of ciliary accumulation is unknown. We generated KIF7 variants with altered microtubule binding or motility. We demonstrate that microtubule binding of KIF7 is not required for the increase in KIF7 or Gli localization at the cilium tip in response to Hedgehog signaling. In addition, we show that the immotile behavior of KIF7 is required to prevent ciliary localization of Gli transcription factors in the absence of Hedgehog signaling. Using an engineered kinesin-2 motor that enables acute inhibition of intraflagellar transport (IFT), we demonstrate that kinesin-2 KIF3A/KIF3B/KAP mediates the translocation of KIF7 to the cilium tip in response to Hedgehog pathway activation. Together, these results suggest that KIF7’s role at the tip of the cilium is unrelated to its ability to bind to microtubules.


2018 ◽  
Vol 29 (10) ◽  
pp. 1178-1189 ◽  
Author(s):  
Thibaut Eguether ◽  
Fabrice P. Cordelieres ◽  
Gregory J. Pazour

The vertebrate hedgehog pathway is organized in primary cilia, and hedgehog components relocate into or out of cilia during signaling. Defects in intraflagellar transport (IFT) typically disrupt ciliary assembly and attenuate hedgehog signaling. Determining whether IFT drives the movement of hedgehog components is difficult due to the requirement of IFT for building cilia. Unlike most IFT proteins, IFT27 is dispensable for cilia formation but affects hedgehog signaling similarly to other IFTs, allowing us to examine its role in the dynamics of signaling. Activating signaling at points along the pathway in Ift27 mutant cells showed that IFT is extensively involved in the pathway. Similar analysis of Bbs mutant cells showed that BBS proteins participate at many levels of signaling but are not needed to concentrate Gli transcription factors at the ciliary tip. Our analysis showed that smoothened delivery to cilia does not require IFT27, but the role of other IFTs is not known. Using a rapamycin-induced dimerization system to sequester IFT-B proteins at the mitochondria in cells with fully formed cilia did not affect the delivery of Smo to cilia, suggesting that this membrane protein may not require IFT-B for delivery.


Pneumologie ◽  
2018 ◽  
Vol 72 (S 01) ◽  
pp. S114-S115
Author(s):  
M Wygrecka ◽  
M Didiasova ◽  
R Singh ◽  
J Wilhelm ◽  
G Kwapiszewska ◽  
...  

2015 ◽  
Vol 11 (8) ◽  
pp. 2190-2197 ◽  
Author(s):  
Wolfgang Schmidt-Heck ◽  
Madlen Matz-Soja ◽  
Susanne Aleithe ◽  
Eugenia Marbach ◽  
Reinhard Guthke ◽  
...  

The Hedgehog signalling-driven Gli transcription factors in hepatocytes form a regulatory network identified by a fuzzy-logic modelling approach. The network explains dynamic features important for hepatocyte function and fate.


Pancreatology ◽  
2013 ◽  
Vol 13 (2) ◽  
pp. e25
Author(s):  
M.G. Fernandez-Barrena ◽  
L.L. Almada ◽  
M.E. Fernandez-Zapico

Nature ◽  
2003 ◽  
Vol 426 (6962) ◽  
pp. 83-87 ◽  
Author(s):  
Danwei Huangfu ◽  
Aimin Liu ◽  
Andrew S. Rakeman ◽  
Noel S. Murcia ◽  
Lee Niswander ◽  
...  

2016 ◽  
Vol 291 (49) ◽  
pp. 25749-25760 ◽  
Author(s):  
Meng Wu ◽  
Lishann Ingram ◽  
Ezequiel J. Tolosa ◽  
Renzo E. Vera ◽  
Qianjin Li ◽  
...  

Cell Cycle ◽  
2010 ◽  
Vol 9 (22) ◽  
pp. 4429-4428
Author(s):  
Alberto Varas ◽  
Rosa Sacedón

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