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TMEM231, mutated in orofaciodigital and Meckel syndromes, organizes the ciliary transition zone

Lookup NU author(s): Professor John SayerORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0).


The Meckel syndrome (MKS) complex functions at the transition zone, located between the basal body and axoneme, to regulate the localization of ciliary membrane proteins. We investigated the role of Tmem231, a two-pass transmembrane protein, in MKS complex formation and function. Consistent with a role in transition zone function, mutation of mouse Tmem231 disrupts the localization of proteins including Arl13b and Inpp5e to cilia, resulting in phenotypes characteristic of MKS such as polydactyly and kidney cysts. Tmem231 and B9d1 are essential for each other and other complex components such as Mks1 to localize to the transition zone. As in mouse, the Caenorhabditis elegans orthologue of Tmem231 localizes to and controls transition zone formation and function, suggesting an evolutionarily conserved role for Tmem231. We identified TMEM231 mutations in orofaciodigital syndrome type 3 (OFD3) and MKS patients that compromise transition zone function. Thus, Tmem231 is critical for organizing the MKS complex and controlling ciliary composition, defects in which cause OFD3 and MKS.

Publication metadata

Author(s): Roberson EC, Dowdle WE, Ozanturk A, Garcia-Gonzalo FR, Li CM, Halbritter J, Elkhartoufi N, Porath JD, Cope H, Ashley-Koch A, Gregory S, Thomas S, Sayer JA, Saunier S, Otto EA, Katsanis N, Davis EE, AttiƩ-Bitach T, Hildebrandt F, Leroux MR, Reiter JF

Publication type: Article

Publication status: Published

Journal: Journal of Cell Biology

Year: 2015

Volume: 209

Issue: 1

Pages: 129-142

Print publication date: 13/04/2015

Acceptance date: 25/02/2015

Date deposited: 05/04/2016

ISSN (print): 0021-9525

ISSN (electronic): 1540-8140

Publisher: Rockerfeller University Press


DOI: 10.1083/jcb.201411087


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Funder referenceFunder name
Canadian Institutes of Health Research
March of Dimes
Sandler Family Supporting Foundation
Achievement Rewards for College Scientists Foundation
Burroughs Wellcome Fund
Michael Smith Foundation for Health Research
Packard Foundation
20100BLAN112202Agence Nationale de la Recherche (ANR)
241955EU seventh FP
ANR-10-IAHY-01investments for the future program
DK072301US National Institutes of Health (NIH)
DEQ20130326532Fondation pour la Recherche Medicale
DK-068306US National Institutes of Health (NIH)
HD042601US National Institutes of Health (NIH)
NS039818US National Institutes of Health (NIH)