NDLI: Role of lipid metabolism in Smoothened de-repression in Hedgehog signaling

Content Provider	PubMed Central
Author	Yavari, Amir Nagaraj, Raghavendra Owusu-ansah, Edward Andrew, Folick Ngo, Kathy Hillman, Tyler Call, Gerald Rohatgi, Rajat Scott, Matthew P. Banerjee, Utpal
Copyright Year	2010
Abstract	The binding of Hedgehog to its receptor Patched causes de-repression of Smoothened resulting in the activation of the Hedgehog pathway. Here, we show that Smo activation is dependent on the levels of phospholipid, Phosphatidyl Inositol-4 Phosphate (PI4P). Loss of STT4 kinase required for the generation of PI4P exhibits hh-loss of function phenotypes while loss of Sac1 phosphatase required for the degradation of PI4P results in hh-gain of function phenotypes in multiple setting during Drosophila development. Furthermore, loss of Ptc function which results in the activation of Hedgehog pathway also causes an increase in PI4P levels. Sac1 functions downstream of STT4 and Ptc in the regulation of Smo membrane localization and Hh pathway activation. Taken together, our results suggest a model in which Ptc directly or indirectly functions to suppress the accumulation of PI4P. Binding of Hh to Ptc derepresses the levels of PI4P, which in turn promotes Smo activation.
Related Links	http://dx.doi.org/10.1016/j.devcel.2010.06.007
Ending Page	65
Page Count	12
Starting Page	54
File Format	PDF
ISSN	15345807
e-ISSN	18781551
Journal	Developmental cell
Issue Number	1
Volume Number	19
Language	English
Publisher Date	2010-07-01
Access Restriction	Open
Subject Keyword	Developmental Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Molecular Biology

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