SSBD - SSBD:database - FIB-SEM490-610

Related paper(s)

Tatsuo Miyamoto, Kosuke Hosoba, Takeshi Itabashi, Atsuko H Iwane, Silvia Natsuko Akutsu, Hiroshi Ochiai, Yumiko Saito, Takashi Yamamoto, Shinya Matsuura (2020) Insufficiency of ciliary cholesterol in hereditary Zellweger syndrome., The EMBO journal, Volume 39, Number 12, pp. e103499

Published in 2020 Jun 17 (Electronic publication in May 5, 2020, midnight )

doi: 10.15252/embj.2019103499
pmid: 32368833

(Abstract) Primary cilia are antenna-like organelles on the surface of most mammalian cells that receive sonic hedgehog (Shh) signaling in embryogenesis and carcinogenesis. Cellular cholesterol functions as a direct activator of a seven-transmembrane oncoprotein called Smoothened (Smo) and thereby induces Smo accumulation on the ciliary membrane where it transduces the Shh signal. However, how cholesterol is supplied to the ciliary membrane remains unclear. Here, we report that peroxisomes are essential for the transport of cholesterol into the ciliary membrane. Zellweger syndrome (ZS) is a peroxisome-deficient hereditary disorder with several ciliopathy-related features and cells from these patients showed a reduced cholesterol level in the ciliary membrane. Reverse genetics approaches revealed that the GTP exchange factor Rabin8, the Rab GTPase Rab10, and the microtubule minus-end-directed kinesin KIFC3 form a peroxisome-associated complex to control the movement of peroxisomes along microtubules, enabling communication between peroxisomes and ciliary pocket membranes. Our findings suggest that insufficient ciliary cholesterol levels may underlie ciliopathies.

(MeSH Terms)

SSBD:database

Detail of FIB-SEM490-610_ciliarymembrane