TY - JOUR
T1 - IFT25 Links the Signal-Dependent Movement of Hedgehog Components to Intraflagellar Transport
AU - Keady, Brian T.
AU - Samtani, Rajeev
AU - Tobita, Kimimasa
AU - Tsuchya, Maiko
AU - San Agustin, Jovenal T.
AU - Follit, John A.
AU - Jonassen, Julie A.
AU - Subramanian, Ramiah
AU - Lo, Cecilia W.
AU - Pazour, Gregory J.
N1 - Funding Information:
We thank Drs. S. Jones (Transgenic Mouse Core), G. Hendricks (Electron Microscopy Core), and P. Furcinitti (Digital Imaging Core) for assistance during this work and Dr. R. Bloodgood for carefully reading the manuscript. We also thank Dr. P. Odgren for use of his bright-field microscope, and Drs. J. Eggenschwiler (Princeton Univ) and R. Rohatgi (Stanford Univ) for reagents. This work was supported by the National Institutes of Health (GM060992 to G.J.P.) and (5U01HL098180 to C.W.L.). Core resources supported by the Diabetes Endocrinology Research Center grant DK32520 were also used.
PY - 2012/5/15
Y1 - 2012/5/15
N2 - 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.
AB - 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.
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U2 - 10.1016/j.devcel.2012.04.009
DO - 10.1016/j.devcel.2012.04.009
M3 - Article
C2 - 22595669
AN - SCOPUS:84860898145
SN - 1534-5807
VL - 22
SP - 940
EP - 951
JO - Developmental Cell
JF - Developmental Cell
IS - 5
ER -