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Lookup NU author(s): Sunitha Balaraju,
Dr Ana TopfORCiD,
Professor Rita HorvathORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2020 The Author(s). Microtubules help building the cytoskeleton of neurons and other cells. Several components of the gamma-tubulin (γ-tubulin) complex have been previously reported in human neurodevelopmental diseases. We describe two siblings from a consanguineous Turkish family with dysmorphic features, developmental delay, brain malformation, and epilepsy carrying a homozygous mutation (p.Glu311Lys) in TUBGCP2 encoding the γ-tubulin complex 2 (GCP2) protein. This variant is predicted to disrupt the electrostatic interaction of GCP2 with GCP3. In primary fibroblasts carrying the variant, we observed a faint delocalization of γ-tubulin during the cell cycle but normal GCP2 protein levels. Through mass spectrometry, we observed dysregulation of multiple proteins involved in the assembly and organization of the cytoskeleton and the extracellular matrix, controlling cellular adhesion and of proteins crucial for neuronal homeostasis including axon guidance. In summary, our functional and proteomic studies link TUBGCP2 and the γ-tubulin complex to the development of the central nervous system in humans.© 2020 The Author(s)Biological Sciences; Neuroscience; Molecular Neuroscience; Clinical Neuroscience; Systems Biology; Protemics
Author(s): Gungor S, Oktay Y, Hiz S, Aranguren-Ibanez A, Kalafatcilar I, Yaramis A, Karaca E, Yis U, Sonmezler E, Ekinci B, Aslan M, Yilmaz E, Ozgor B, Balaraju S, Szabo N, Laurie S, Beltran S, MacArthur DG, Hathazi D, Topf A, Roos A, Lochmuller H, Vernos I, Horvath R
Publication type: Article
Publication status: Published
Print publication date: 22/01/2021
Online publication date: 14/12/2020
Acceptance date: 11/12/2020
Date deposited: 22/08/2023
ISSN (electronic): 2589-0042
Publisher: Elsevier Inc.
Data Access Statement: All genetic data have been deposited in the EGA database and in RD-CONNECT under the following ID numbers: patient 1: E497133, patient 2: E477343, mother: E615258, father: E739679, unaffected sibling: E191145. These data can be made available after an authentication process.
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