Abstract :
[en] Primary cilia interpret vertebrate Hedgehog (Hh) signals. Why cilia are essential for
signaling is unclear. One possibility is that some forms of signaling require a distinct
membrane lipid composition, found at cilia. We found that the ciliary membrane
contains a particular phosphoinositide, PI(4)P, whereas a different phosphoinositide,
PI(4,5)P2, is restricted to the membrane of the ciliary base. This distribution is created
by Inpp5e, a ciliary phosphoinositide 5-phosphatase. Without Inpp5e, ciliary PI(4,5)P2
levels are elevated and Hh signaling is disrupted. Inpp5e limits the ciliary level
s of inhibitors of Hh signaling, including Gpr161 and the PI(4,5)2-binding protein Tulp3.
Increasing ciliary PI(4,5)P2levels or conferring the ability to bind PI(4)P on Tulp3
increases the ciliary localization of Tulp3. Lowering Tulp3 in cells lacking Inpp5e
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