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Mutations in GDAP1 Influence Structure and Function of the Trans-Golgi Network

Binienda, Katarzyna and Rzepnikowska, Weronika and Kolakowski, Damian and Kaminska, Joanna and Szczepankiewicz, Andrzej Antoni and Nieznańska, Hanna and Kochański, Andrzej and Kabzińska, Dagmara (2021) Mutations in GDAP1 Influence Structure and Function of the Trans-Golgi Network. International Journal of Molecular Sciences . ISSN 1422-0067


Official URL: https://www.mdpi.com/1422-0067/22/2/914


Charcot-Marie-Tooth disease (CMT) is a heritable neurodegenerative disease that displays great genetic heterogeneity. The genes and mutations that underlie this heterogeneity have been extensively characterized by molecular genetics. However, the molecular pathogenesis of the vast majority of CMT subtypes remains terra incognita. Any attempts to perform experimental therapy for CMT disease are limited by a lack of understanding of the pathogenesis at a molecular level. In this study, we aim to identify the molecular pathways that are disturbed by mutations in the gene encoding GDAP1 using both yeast and human cell, based models of CMT-GDAP1 disease. We found that some mutations in GDAP1 led to a reduced expression of the GDAP1 protein and resulted in a selective disruption of the Golgi apparatus. These structural alterations are accompanied by functional disturbances within the Golgi. We screened over 1500 drugs that are available on the market using our yeast-based CMT-GDAP1 model. Drugs were identified that had both positive and negative effects on cell phenotypes. To the best of our knowledge, this study is the first report of the Golgi apparatus playing a role in the pathology of CMT disorders. The drugs we identified, using our yeast-based CMT-GDAP1 model, may be further used in translational research.

Item Type:Article
Subjects:Q Science > Q Science (General)
Divisions:Department of Genetics
ID Code:1992
Deposited By: PhD Joanna Kamińska
Deposited On:15 Feb 2021 08:58
Last Modified:16 Feb 2021 08:25

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