Article (Scientific journals)
INPP5E controls ciliary localization of phospholipids and odor response in olfactory sensory neurons
Ukhavov, K.; Uytingco, C.; Green, W. et al.
2022In Journal of Cell Science, 135 (5)
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Keywords :
Inpp5e; 5-phosphatase; phosphoinositides; primary cilium; Joubert syndrome; olfaction
Abstract :
[en] Ciliopathies manifested in part by a dysfunction of several phosphoinositide 5’phosphatases constitute Lowes, Dent disease 2 and Joubert syndromes through critical involvement of properly functioning primary cilia (PC). We showed that deletion of INPP5E under the control of OMP-Cre in mature mouse olfactory sensory neurons (OSNs) led to a dramatic redistribution of PI(4,5)P2 (PIP2) in cilia, significant reduction of PI(3,4)P2 and enrichment of PI(3,4,5)P3 in knobs. Redistribution of the phospholipids accompanied marked elongation of cilia in INPP5E-OMP knockout (KO) OSNs. Such a dramatic remodeling of phospholipid composition however did not affect other integral membrane lipids (cholesterol, sphingomyelin, glycosylated phosphaditylinositol, phosphatidylserine). Proteins known to bind with high affinity PIP2 entered the cilia of the KO OSNs. Loss of INPP5E did not affect ciliary localization of endogenous olfactory receptor M71/M72 or distribution and movement of IFT122 particles implicating independent of phospholipids mechanism of retrograde protein transport in cilia of mature OSNs. Net odor sensitivity and response magnitude as measured by EOG was not affected by the mutation. However, odor adaptation in the KO mouse was significantly impaired resulting in less efficient recovery and altered inactivation kinetics of the odor response at the EOG and single-cell level. These findings implicate phosphoinositide-dependent regulation of active Ca2+ extrusion in OSNs whereby controlling the rate of sensory adaptation.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Ukhavov, K.
Uytingco, C.
Green, W.
Zhang, L.
Schurmans, Stéphane  ;  Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > Biochimie métabolique vétérinaire
Martens, J. R.
Language :
Title :
INPP5E controls ciliary localization of phospholipids and odor response in olfactory sensory neurons
Publication date :
01 March 2022
Journal title :
Journal of Cell Science
Publisher :
The Company of Biologists, United Kingdom
Volume :
Issue :
Peer reviewed :
Peer Reviewed verified by ORBi
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