Home LiteratureArticle Details
PMID: 22595669 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

IFT25 links the signal-dependent movement of Hedgehog components to intraflagellar transport.

Developmental cell ·Vol. 22 ·No. 5 ·2012-05-15 ·Pages 940-51

Keady BT, Samtani R, Tobita K, Tsuchya M, San Agustin JT, Follit JA, Jonassen JA, Subramanian R, Lo CW, Pazour GJ

Abstract

The intraflagellar transport (IFT) system is required for building primary cilia, sensory organelles that cells use to respond to their environment. IFT particles are composed of about 20 proteins, and these proteins are highly conserved across ciliated species. IFT25, however, is absent from some ciliated organisms, suggesting that it may have a unique role distinct from ciliogenesis. Here, we generate an Ift25 null mouse and show that IFT25 is not required for ciliary assembly but is required for proper Hedgehog signaling, which in mammals occurs within cilia. Mutant mice die at birth with multiple phenotypes, indicative of Hedgehog signaling dysfunction. Cilia lacking IFT25 have defects in the signal-dependent transport of multiple Hedgehog components including Patched-1, Smoothened, and Gli2, and fail to activate the pathway upon stimulation. Thus, IFT function is not restricted to building cilia where signaling occurs, but also plays a separable role in signal transduction events.

MeSH Terms
Animals Biological Transport Cell Culture Techniques Cilia/metabolism Flagella/metabolism Gene Expression Regulation, Developmental Hedgehog Proteins/genetics,metabolism Intracellular Signaling Peptides and Proteins/genetics,metabolism Kruppel-Like Transcription Factors/genetics,metabolism Mice Mice, Inbred C57BL Mice, Knockout Patched Receptors Patched-1 Receptor Receptors, Cell Surface/genetics,metabolism Receptors, G-Protein-Coupled/genetics,metabolism Signal Transduction Smoothened Receptor Zinc Finger Protein Gli2
Chemicals
Gli2 protein, mouse Hedgehog Proteins IFT25 protein, mouse Intracellular Signaling Peptides and Proteins Kruppel-Like Transcription Factors Patched Receptors Patched-1 Receptor Ptch1 protein, mouse Receptors, Cell Surface Receptors, G-Protein-Coupled Smo protein, mouse Smoothened Receptor Zinc Finger Protein Gli2
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Keady Brian T
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Samtani Rajeev
Tobita Kimimasa
Tsuchya Maiko
San Agustin Jovenal T
Follit John A
Jonassen Julie A
Subramanian Ramiah
Lo Cecilia W
Pazour Gregory J
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Article Info
Journal
Developmental cell
Abbr.
Dev Cell
ISSN
1878-1551
DOI
10.1016/j.devcel.2012.04.009
Published
2012-05-15
Pages
940-51
Language
English
Region
United States
NLM ID
101120028
PMCID
PMC3366633
Subset
IM
Grants
NIGMS NIH HHS · GM060992 · United States
NHLBI NIH HHS · 5U01HL098180 · United States
NIDDK NIH HHS · P30 DK032520 · United States
NIDDK NIH HHS · DK32520 · United States
NHLBI NIH HHS · U01 HL098180 · United States
NIGMS NIH HHS · R01 GM060992 · United States
External Links
PubMed source DOI: 10.1016/j.devcel.2012.04.009 PMC Full Text View journal details
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