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Biomedicines
Volume 11
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10.3390/biomedicines11010146
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Article

Impact of Hypermannosylation on the Structure and Functionality of the ER and the Golgi Complex

by
Patricia Franzka
1,*,
Svenja Caren Schüler
2,
Takfarinas Kentache
3,
Robert Storm
4,
Andrea Bock
1,
Istvan Katona
5,
Joachim Weis
5,
Katrin Buder
2,
Christoph Kaether
2 and
Christian A. Hübner
1,*
1
Institute of Human Genetics, University Hospital Jena, 07747 Jena, Germany
2
Leibniz-Institute on Aging—Fritz-Lipmann-Institute, 07745 Jena, Germany
3
De Duve Institute, UCLouvain, BE-1200 Woluwe-Saint-Lambert, Belgium
4
Molecular Devices, 81377 München, Germany
5
Institute of Neuropathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
*
Authors to whom correspondence should be addressed.
Biomedicines 2023, 11(1), 146; https://doi.org/10.3390/biomedicines11010146
Submission received: 3 October 2022 / Revised: 20 December 2022 / Accepted: 29 December 2022 / Published: 6 January 2023
(This article belongs to the Special Issue Biochemical and Cellular Mechanisms Regulating ER-to-Golgi Vesicular Trafficking in Health and Disease)
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Abstract

Proteins of the secretory pathway undergo glycosylation in the endoplasmic reticulum (ER) and the Golgi apparatus. Altered protein glycosylation can manifest in serious, sometimes fatal malfunctions. We recently showed that mutations in GDP-mannose pyrophosphorylase A (GMPPA) can cause a syndrome characterized by alacrima, achalasia, mental retardation, and myopathic alterations (AAMR syndrome). GMPPA acts as a feedback inhibitor of GDP-mannose pyrophosphorylase B (GMPPB), which provides GDP-mannose as a substrate for protein glycosylation. Loss of GMPPA thus enhances the incorporation of mannose into glycochains of various proteins, including α-dystroglycan (α-DG), a protein that links the extracellular matrix with the cytoskeleton. Here, we further characterized the consequences of loss of GMPPA for the secretory pathway. This includes a fragmentation of the Golgi apparatus, which comes along with a regulation of the abundance of several ER- and Golgi-resident proteins. We further show that the activity of the Golgi-associated endoprotease furin is reduced. Moreover, the fraction of α-DG, which is retained in the ER, is increased. Notably, WT cells cultured at a high mannose concentration display similar changes with increased retention of α-DG, altered structure of the Golgi apparatus, and a decrease in furin activity. In summary, our data underline the importance of a balanced mannose homeostasis for the secretory pathway.
Keywords: Golgi network; endoplasmic reticulum; mannosylation Golgi network; endoplasmic reticulum; mannosylation

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MDPI and ACS Style

Franzka, P.; Schüler, S.C.; Kentache, T.; Storm, R.; Bock, A.; Katona, I.; Weis, J.; Buder, K.; Kaether, C.; Hübner, C.A. Impact of Hypermannosylation on the Structure and Functionality of the ER and the Golgi Complex. Biomedicines 2023, 11, 146. https://doi.org/10.3390/biomedicines11010146

AMA Style

Franzka P, Schüler SC, Kentache T, Storm R, Bock A, Katona I, Weis J, Buder K, Kaether C, Hübner CA. Impact of Hypermannosylation on the Structure and Functionality of the ER and the Golgi Complex. Biomedicines. 2023; 11(1):146. https://doi.org/10.3390/biomedicines11010146

Chicago/Turabian Style

Franzka, Patricia, Svenja Caren Schüler, Takfarinas Kentache, Robert Storm, Andrea Bock, Istvan Katona, Joachim Weis, Katrin Buder, Christoph Kaether, and Christian A. Hübner. 2023. "Impact of Hypermannosylation on the Structure and Functionality of the ER and the Golgi Complex" Biomedicines 11, no. 1: 146. https://doi.org/10.3390/biomedicines11010146

APA Style

Franzka, P., Schüler, S. C., Kentache, T., Storm, R., Bock, A., Katona, I., Weis, J., Buder, K., Kaether, C., & Hübner, C. A. (2023). Impact of Hypermannosylation on the Structure and Functionality of the ER and the Golgi Complex. Biomedicines, 11(1), 146. https://doi.org/10.3390/biomedicines11010146

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