Moreira, DDP, Suzuki, AM, Silva, ALTE, Varella-Branco, E, Meneghetti, MCZ, Kobayashi, GS, Fogo, M, Ferrari, MDFR, Cardoso, RR, Lourenço, NCV, Griesi-Oliveira, K, Zachi, EC, Bertola, DR, Weinmann, KDS, de Lima, MA ORCID: https://orcid.org/0000-0002-8952-3080, Nader, HB, Sertié, AL and Passos-Bueno, MR (2022) Neuroprogenitor Cells From Patients With TBCK Encephalopathy Suggest Deregulation of Early Secretory Vesicle Transport. Frontiers in Cellular Neuroscience, 15.

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Abstract

<jats:p>Biallelic pathogenic variants in TBCK cause encephaloneuropathy, infantile hypotonia with psychomotor retardation, and characteristic facies 3 (IHPRF3). The molecular mechanisms underlying its neuronal phenotype are largely unexplored. In this study, we reported two sisters, who harbored biallelic variants in TBCK and met diagnostic criteria for IHPRF3. We provided evidence that TBCK may play an important role in the early secretory pathway in neuroprogenitor cells (iNPC) differentiated from induced pluripotent stem cells (iPSC). Lack of functional TBCK protein in iNPC is associated with impaired endoplasmic reticulum-to-Golgi vesicle transport and autophagosome biogenesis, as well as altered cell cycle progression and severe impairment in the capacity of migration. Alteration in these processes, which are crucial for neurogenesis, neuronal migration, and cytoarchitecture organization, may represent an important causative mechanism of both neurodevelopmental and neurodegenerative phenotypes observed in IHPRF3. Whether reduced mechanistic target of rapamycin (mTOR) signaling is secondary to impaired TBCK function over other secretory transport regulators still needs further investigation.</jats:p>

Item Type: Article
Additional Information: Copyright © 2022 Moreira, Suzuki, Silva, Varella-Branco, Meneghetti, Kobayashi, Fogo, Ferrari, Cardoso, Lourenço, Griesi-Oliveira, Zachi, Bertola, Weinmann, Lima, Nader, Sertié and Passos-Bueno. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Subjects: Q Science > QD Chemistry > QD415 Biochemistry
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Natural Sciences > School of Life Sciences
Depositing User: Symplectic
Date Deposited: 19 Jan 2022 15:48
Last Modified: 19 Jan 2022 15:48
URI: https://eprints.keele.ac.uk/id/eprint/10519

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