Please use this identifier to cite or link to this item:
Title: Patched 1 reduces the accessibility of cholesterol in the outer leaflet of membranes
Authors: Kinnebrew, Maia
Luchetti, Giovanni
Sircar, Ria
Frigui, Sara
Viti, Lucrezia Vittoria
Naito, Tomoki
Beckert, Francis
Saheki, Yasunori
Siebold, Christian
Radhakrishnan, Arun
Rohatgi, Rajat
Keywords: Science::Medicine
Issue Date: 2021
Source: Kinnebrew, M., Luchetti, G., Sircar, R., Frigui, S., Viti, L. V., Naito, T., Beckert, F., Saheki, Y., Siebold, C., Radhakrishnan, A. & Rohatgi, R. (2021). Patched 1 reduces the accessibility of cholesterol in the outer leaflet of membranes. ELife, 10, 70504-.
Project: MOE2017-T2-2-001 
Journal: eLife 
Abstract: A long-standing mystery in vertebrate Hedgehog signaling is how Patched 1 (PTCH1), the receptor for Hedgehog ligands, inhibits the activity of Smoothened, the protein that transmits the signal across the membrane. We previously proposed (Kinnebrew et al., 2019) that PTCH1 inhibits Smoothened by depleting accessible cholesterol from the ciliary membrane. Using a new imaging-based assay to directly measure the transport activity of PTCH1, we find that PTCH1 depletes accessible cholesterol from the outer leaflet of the plasma membrane. This transport activity is terminated by binding of Hedgehog ligands to PTCH1 or by dissipation of the transmembrane potassium gradient. These results point to the unexpected model that PTCH1 moves cholesterol from the outer to the inner leaflet of the membrane in exchange for potassium ion export in the opposite direction. Our study provides a plausible solution for how PTCH1 inhibits SMO by changing the organization of cholesterol in membranes and establishes a general framework for studying how proteins change cholesterol accessibility to regulate membrane-dependent processes in cells.
ISSN: 2050-084X
DOI: 10.7554/eLife.70504
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: © 2021 Kinnebrew et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

Files in This Item:
File Description SizeFormat 
elife-70504-v2.pdf2.12 MBAdobe PDFThumbnail

Citations 20

Updated on Sep 23, 2023

Web of ScienceTM
Citations 20

Updated on Sep 24, 2023

Page view(s)

Updated on Sep 30, 2023


Updated on Sep 30, 2023

Google ScholarTM




Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.