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PMID: 22689656 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The IFT-A complex regulates Shh signaling through cilia structure and membrane protein trafficking.

The Journal of cell biology ·Vol. 197 ·No. 6 ·2012-06-11 ·Pages 789-800

Liem KF, Ashe A, He M, Satir P, Moran J, Beier D, Wicking C, Anderson KV

Abstract

Two intraflagellar transport (IFT) complexes, IFT-A and IFT-B, build and maintain primary cilia and are required for activity of the Sonic hedgehog (Shh) pathway. A weak allele of the IFT-A gene, Ift144, caused subtle defects in cilia structure and ectopic activation of the Shh pathway. In contrast, strong loss of IFT-A, caused by either absence of Ift144 or mutations in two IFT-A genes, blocked normal ciliogenesis and decreased Shh signaling. In strong IFT-A mutants, the Shh pathway proteins Gli2, Sufu, and Kif7 localized correctly to cilia tips, suggesting that these pathway components were trafficked by IFT-B. In contrast, the membrane proteins Arl13b, ACIII, and Smo failed to localize to primary cilia in the absence of IFT-A. We propose that the increased Shh activity seen in partial loss-of-function IFT-A mutants may be a result of decreased ciliary ACIII and that the loss of Shh activity in the absence of IFT-A is a result of severe disruptions of cilia structure and membrane protein trafficking.

MeSH Terms
Animals Cilia/metabolism,ultrastructure Cytoskeletal Proteins Flagella/metabolism Hedgehog Proteins/genetics,metabolism Intracellular Signaling Peptides and Proteins/genetics,metabolism Kinesins/genetics,metabolism Kruppel-Like Transcription Factors/genetics,metabolism Male Membrane Proteins/genetics,metabolism Mice Mice, Inbred C57BL Microscopy, Electron Proteins/genetics,metabolism Repressor Proteins/genetics,metabolism Signal Transduction Zinc Finger Protein Gli2
Chemicals
Cytoskeletal Proteins Gli2 protein, mouse Hedgehog Proteins Intracellular Signaling Peptides and Proteins Kruppel-Like Transcription Factors Membrane Proteins Proteins Repressor Proteins Sufu protein, mouse Wdr19 protein, mouse Zinc Finger Protein Gli2 Kif7 protein, mouse Kinesins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Liem Karel F
Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
Ashe Alyson
He Mu
Satir Peter
Moran Jennifer
Beier David
Wicking Carol
Anderson Kathryn V
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.201110049
Published
2012-06-11
Pages
789-800
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC3373400
Subset
IM
Grants
NINDS NIH HHS · R01 NS044385 · United States
NICHD NIH HHS · U01 HD043430 · United States
Wellcome Trust · 092096 · United Kingdom
NICHD NIH HHS · HD43430 · United States
NINDS NIH HHS · NS044385 · United States
External Links
PubMed source DOI: 10.1083/jcb.201110049 PMC Full Text View journal details
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