Universität zu Köln

Bilican, Saygın ORCID: 0000-0001-9448-6504, Nabawi, Yara, Zhang, William Hongyu ORCID: 0000-0002-2191-3576, Petrovic, Dunja, Wehrmann, Markus ORCID: 0000-0001-7511-7471, Muñoz‐García, Sara ORCID: 0009-0003-4126-7238, Koyuncu, Seda and Vilchez, David ORCID: 0000-0002-0801-0743 (2025). C9orf72 ALS-causing mutations lead to mislocalization and aggregation of nucleoporin Nup107 into stress granules. FEBS Letters, 599 (21). pp. 3047-3065. Wiley. ISSN 0014-5793

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Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal disorder caused by motor neuron degeneration. Hexanucleotide repeat expansions in the C9orf72 gene, the most common genetic cause of ALS (C9‐ALS), drive toxicity through different mechanisms. These pathological changes include alterations in stress granules (SGs), ribonucleoprotein complexes formed under stress conditions. Here, we show that G3BP1, a core component of SGs, exhibits enhanced interaction with the nucleoporin Nup107 in motor neurons derived from patient iPSCs carrying C9orf72 mutations. Moreover, Nup107 colocalizes with SGs and aggregates in C9‐ALS motor neurons. Notably, knockdown of npp‐5 , the Caenorhabditis elegans ortholog of Nup107, alleviates ALS‐associated phenotypes in worm models, including reduced lifespan and impaired motility. Together, our findings provide insights into disease‐related changes in C9‐ALS pathogenesis.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Bilican, Saygın UNSPECIFIED https://orcid.org/0000-0001-9448-6504 UNSPECIFIED Nabawi, Yara UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhang, William Hongyu UNSPECIFIED https://orcid.org/0000-0002-2191-3576 UNSPECIFIED Petrovic, Dunja UNSPECIFIED UNSPECIFIED UNSPECIFIED Wehrmann, Markus UNSPECIFIED https://orcid.org/0000-0001-7511-7471 UNSPECIFIED Muñoz‐García, Sara UNSPECIFIED https://orcid.org/0009-0003-4126-7238 UNSPECIFIED Koyuncu, Seda UNSPECIFIED UNSPECIFIED UNSPECIFIED Vilchez, David UNSPECIFIED https://orcid.org/0000-0002-0801-0743 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-805043
Identification Number:	10.1002/1873-3468.70156
Journal or Publication Title:	FEBS Letters
Volume:	599
Number:	21
Page Range:	pp. 3047-3065
Number of Pages:	19
Date:	November 2025
Publisher:	Wiley
ISSN:	0014-5793
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics Zentrum für Molekulare Medizin
Subjects:	Life sciences Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Amyotrophic lateral sclerosis ; C. elegans ; iPSC-disease modeling ; Nucleoporins ; Proteostasis ; Stress granules English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/80504