SorCS2 binds progranulin to regulate motor neuron development.

Autor:	Thomasen PB; Danish Research Institute of Translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine, and Center of Excellence PROMEMO, 8000 Aarhus C, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Salasova A; Danish Research Institute of Translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine, and Center of Excellence PROMEMO, 8000 Aarhus C, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark. Electronic address: alena.salasova@biomed.au.dk., Kjaer-Sorensen K; Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark., Woloszczuková L; Danish Research Institute of Translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine, and Center of Excellence PROMEMO, 8000 Aarhus C, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Lavický J; Department of Histology and Embryology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic., Login H; Danish Research Institute of Translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine, and Center of Excellence PROMEMO, 8000 Aarhus C, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Tranberg-Jensen J; Danish Research Institute of Translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine, and Center of Excellence PROMEMO, 8000 Aarhus C, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Almeida S; Danish Research Institute of Translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine, and Center of Excellence PROMEMO, 8000 Aarhus C, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Beel S; Department of Neurology and Department of Neurosciences, KU Leuven and Center for Brain & Disease Research VIB, 3000 Leuven, Belgium., Kavková M; Department of Histology and Embryology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic., Qvist P; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Kjolby M; Danish Research Institute of Translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine, and Center of Excellence PROMEMO, 8000 Aarhus C, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Ovesen PL; Danish Research Institute of Translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine, and Center of Excellence PROMEMO, 8000 Aarhus C, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Nolte S; Danish Research Institute of Translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine, and Center of Excellence PROMEMO, 8000 Aarhus C, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Vestergaard B; Danish Research Institute of Translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine, and Center of Excellence PROMEMO, 8000 Aarhus C, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Udrea AC; Danish Research Institute of Translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine, and Center of Excellence PROMEMO, 8000 Aarhus C, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark., Nejsum LN; Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark., Chao MV; Department of Neuroscience and Physiology, NYU Langone Health, New York, NY 10016, USA., Van Damme P; Department of Neurology and Department of Neurosciences, KU Leuven and Center for Brain & Disease Research VIB, 3000 Leuven, Belgium., Krivanek J; Department of Histology and Embryology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic., Dasen J; Department of Neuroscience and Physiology, NYU Langone Health, New York, NY 10016, USA., Oxvig C; Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark., Nykjaer A; Danish Research Institute of Translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine, and Center of Excellence PROMEMO, 8000 Aarhus C, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark. Electronic address: an@biomed.au.dk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Nov 28; Vol. 42 (11), pp. 113333. Date of Electronic Publication: 2023 Oct 27.
DOI:	10.1016/j.celrep.2023.113333
Abstrakt:	Motor neuron (MN) development and nerve regeneration requires orchestrated action of a vast number of molecules. Here, we identify SorCS2 as a progranulin (PGRN) receptor that is required for MN diversification and axon outgrowth in zebrafish and mice. In zebrafish, SorCS2 knockdown also affects neuromuscular junction morphology and fish motility. In mice, SorCS2 and PGRN are co-expressed by newborn MNs from embryonic day 9.5 until adulthood. Using cell-fate tracing and nerve segmentation, we find that SorCS2 deficiency perturbs cell-fate decisions of brachial MNs accompanied by innervation deficits of posterior nerves. Additionally, adult SorCS2 knockout mice display slower motor nerve regeneration. Interestingly, primitive macrophages express high levels of PGRN, and their interaction with SorCS2-positive motor axon is required during axon pathfinding. We further show that SorCS2 binds PGRN to control its secretion, signaling, and conversion into granulins. We propose that PGRN-SorCS2 signaling controls MN development and regeneration in vertebrates. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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