Universität zu Köln

Przyklenk, Matthias, Karmacharya, Shreya, Bonasera, Debora ORCID: 0000-0003-1567-2283, Pasanen-Zentz, Arthur-Lauri ORCID: 0000-0002-0012-2601, Kmoch, Stanislav, Paulsson, Mats ORCID: 0000-0002-6846-857X, Wagener, Raimund ORCID: 0000-0003-3186-017X, Liccardi, Gianmaria ORCID: 0000-0002-2662-1281 and Schiavinato, Alvise ORCID: 0000-0002-8969-4074 (2024). ANTXR1 deficiency promotes fibroblast senescence: implications for GAPO syndrome as a progeroid disorder. Scientific Reports, 14 (1). pp. 1-14. Springer Nature. ISSN 2045-2322

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Abstract

[Artikel-Nr.: 9321] ANTXR1 is one of two cell surface receptors mediating the uptake of the anthrax toxin into cells. Despite substantial research on its role in anthrax poisoning and a proposed function as a collagen receptor, ANTXR1’s physiological functions remain largely undefined. Pathogenic variants in ANTXR1 lead to the rare GAPO syndrome, named for its four primary features: Growth retardation, Alopecia, Pseudoanodontia, and Optic atrophy. The disease is also associated with a complex range of other phenotypes impacting the cardiovascular, skeletal, pulmonary and nervous systems. Aberrant accumulation of extracellular matrix components and fibrosis are considered to be crucial components in the pathogenesis of GAPO syndrome, contributing to the shortened life expectancy of affected individuals. Nonetheless, the specific mechanisms connecting ANTXR1 deficiency to the clinical manifestations of GAPO syndrome are largely unexplored. In this study, we present evidence that ANTXR1 deficiency initiates a senescent phenotype in human fibroblasts, correlating with defects in nuclear architecture and actin dynamics. We provide novel insights into ANTXR1's physiological functions and propose GAPO syndrome to be reconsidered as a progeroid disorder highlighting an unexpected role for an integrin-like extracellular matrix receptor in human aging. aschiav1@uni-koeln.de ANTXR1 is one of two cell surface receptors mediating the uptake of the anthrax toxin into cells. Despite substantial research on its role in anthrax poisoning and a proposed function as a collagen receptor, ANTXR1’s physiological functions remain largely undefined. Pathogenic variants in ANTXR1 lead to the rare GAPO syndrome, named for its four primary features: Growth retardation, Alopecia, Pseudoanodontia, and Optic atrophy. The disease is also associated with a complex range of other phenotypes impacting the cardiovascular, skeletal, pulmonary and nervous systems. Aberrant accumulation of extracellular matrix components and fibrosis are considered to be crucial components in the pathogenesis of GAPO syndrome, contributing to the shortened life expectancy of affected individuals. Nonetheless, the specific mechanisms connecting ANTXR1 deficiency to the clinical manifestations of GAPO syndrome are largely unexplored. In this study, we present evidence that ANTXR1 deficiency initiates a senescent phenotype in human fibroblasts, correlating with defects in nuclear architecture and actin dynamics. We provide novel insights into ANTXR1's physiological functions and propose GAPO syndrome to be reconsidered as a progeroid disorder highlighting an unexpected role for an integrin-like extracellular matrix receptor in human aging.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Przyklenk, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Karmacharya, Shreya UNSPECIFIED UNSPECIFIED UNSPECIFIED Bonasera, Debora UNSPECIFIED https://orcid.org/0000-0003-1567-2283 UNSPECIFIED Pasanen-Zentz, Arthur-Lauri UNSPECIFIED https://orcid.org/0000-0002-0012-2601 UNSPECIFIED Kmoch, Stanislav UNSPECIFIED UNSPECIFIED UNSPECIFIED Paulsson, Mats UNSPECIFIED https://orcid.org/0000-0002-6846-857X UNSPECIFIED Wagener, Raimund UNSPECIFIED https://orcid.org/0000-0003-3186-017X UNSPECIFIED Liccardi, Gianmaria UNSPECIFIED https://orcid.org/0000-0002-2662-1281 UNSPECIFIED Schiavinato, Alvise UNSPECIFIED https://orcid.org/0000-0002-8969-4074 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-815407
Identification Number:	10.1038/s41598-024-59901-y
Journal or Publication Title:	Scientific Reports
Volume:	14
Number:	1
Page Range:	pp. 1-14
Number of Pages:	14
Date:	23 April 2024
Publisher:	Springer Nature
ISSN:	2045-2322
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Biochemie > Zentrum für Biochemie Faculty of Medicine > Kinder- und Jugendmedizin > Klinik und Poliklinik für Kinder- und Jugendmedizin Zentrum für Molekulare Medizin
Subjects:	Life sciences Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81540