Oct 23, 2018

INPP5E controls ciliary localization of phospholipids and odor response kinetics in a mouse model of Joubert syndrome

BioRxiv : the Preprint Server for Biology
Kirill UkhanovJeffrey R Martens

Abstract

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 si...Continue Reading

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Mentioned in this Paper

Establishment and Maintenance of Localization
INPP5E gene
Phosphatidylinositols
Dent Disease 2
Phosphoric Monoester Hydrolases
Phosphatidylserines
Regulation of Biological Process
Pancreatic Carcinoma
Familial Aplasia of the Vermis
Knock-out

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