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Cells
Volume 14
Issue 17
10.3390/cells14171355
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Deciphering α-L-Fucosidase Activity Contribution in Human and Mouse: Tissue α-L-Fucosidase FUCA1 Meets Plasma α-L-Fucosidase FUCA2

by
Hannah Bäumges
1,
Svenja Jelinek
1,
Heike Lange
1,
Sandra Markmann
2,
Emanuela Capriotti
2,
Jan Anwar Häusser
1,
Mai-Britt Ilse
1,
Thomas Braulke
2 and
Torben Lübke
1,*
1
Department of Chemistry, Biochemistry III, Bielefeld University, 33615 Bielefeld, Germany
2
Institute of Osteology & Biomechanics, Cell Biology of Rare Diseases, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
*
Author to whom correspondence should be addressed.
Cells 2025, 14(17), 1355; https://doi.org/10.3390/cells14171355 (registering DOI)
Submission received: 13 April 2025 / Revised: 17 August 2025 / Accepted: 27 August 2025 / Published: 30 August 2025
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Lysosomal Storage Disorders)
Versions Notes

Abstract

Fucose-containing glycoproteins and glycolipids broadly occur in humans as well as in many other species and are essential for a wide range of physiological processes, such as cell adhesion, fertilization, and tumor development. In humans, the cellular degradation of various fucosylated glycoconjugates depends on the FUCA1-encoded lysosomal tissue α-L-fucosidase (FUCA1). The crucial role of FUCA1 is reflected by the severe lysosomal storage disease fucosidosis, which causes a massive accumulation of fucosylated glycans, glycolipids, and α(1,6)-fucosylated glycoasparagines. Therefore, it is reasonable to assume that FUCA1 is predominantly responsible for the degradation of fucosylated glycoconjugates, although a second, functionally uncharacterized α-L-fucosidase, the plasma α-L-fucosidase (FUCA2), is known. To investigate the impact of both fucosidases in more detail, we generated two different monoclonal antibodies as useful tools for the detection of human and murine FUCA1 and utilized a FUCA2-specific antibody to demonstrate that FUCA2 is a bona fide lysosomal protein that is sorted in a mannose 6-phosphate (M6P)-dependent manner. We then compared FUCA1 and FUCA2 upon ectopic expression and evaluated their enzyme activity profiles under various conditions. Untagged and differently tagged versions of FUCA1 exhibited α-L-fucosidase activity, while various FUCA2 derivatives, even after affinity purification, did not show any fucosidase activity against commonly used pseudo-substrates. Our findings suggest that FUCA1 and not FUCA2 is exclusively responsible for the lysosomal de-fucosylation of glycoconjugates.
Keywords: α-L-fucosidase 1; FUCA1; α-L-fucosidase 2; FUCA2; lysosomes; lysosomal storage disease; fucosidosis α-L-fucosidase 1; FUCA1; α-L-fucosidase 2; FUCA2; lysosomes; lysosomal storage disease; fucosidosis

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MDPI and ACS Style

Bäumges, H.; Jelinek, S.; Lange, H.; Markmann, S.; Capriotti, E.; Häusser, J.A.; Ilse, M.-B.; Braulke, T.; Lübke, T. Deciphering α-L-Fucosidase Activity Contribution in Human and Mouse: Tissue α-L-Fucosidase FUCA1 Meets Plasma α-L-Fucosidase FUCA2. Cells 2025, 14, 1355. https://doi.org/10.3390/cells14171355

AMA Style

Bäumges H, Jelinek S, Lange H, Markmann S, Capriotti E, Häusser JA, Ilse M-B, Braulke T, Lübke T. Deciphering α-L-Fucosidase Activity Contribution in Human and Mouse: Tissue α-L-Fucosidase FUCA1 Meets Plasma α-L-Fucosidase FUCA2. Cells. 2025; 14(17):1355. https://doi.org/10.3390/cells14171355

Chicago/Turabian Style

Bäumges, Hannah, Svenja Jelinek, Heike Lange, Sandra Markmann, Emanuela Capriotti, Jan Anwar Häusser, Mai-Britt Ilse, Thomas Braulke, and Torben Lübke. 2025. "Deciphering α-L-Fucosidase Activity Contribution in Human and Mouse: Tissue α-L-Fucosidase FUCA1 Meets Plasma α-L-Fucosidase FUCA2" Cells 14, no. 17: 1355. https://doi.org/10.3390/cells14171355

APA Style

Bäumges, H., Jelinek, S., Lange, H., Markmann, S., Capriotti, E., Häusser, J. A., Ilse, M.-B., Braulke, T., & Lübke, T. (2025). Deciphering α-L-Fucosidase Activity Contribution in Human and Mouse: Tissue α-L-Fucosidase FUCA1 Meets Plasma α-L-Fucosidase FUCA2. Cells, 14(17), 1355. https://doi.org/10.3390/cells14171355

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