Cell Reports (Nov 2023)
SorCS2 binds progranulin to regulate motor neuron development
- Pernille Bogetofte Thomasen,
- Alena Salasova,
- Kasper Kjaer-Sorensen,
- Lucie Woloszczuková,
- Josef Lavický,
- Hande Login,
- Jeppe Tranberg-Jensen,
- Sergio Almeida,
- Sander Beel,
- Michaela Kavková,
- Per Qvist,
- Mads Kjolby,
- Peter Lund Ovesen,
- Stella Nolte,
- Benedicte Vestergaard,
- Andreea-Cornelia Udrea,
- Lene Niemann Nejsum,
- Moses V. Chao,
- Philip Van Damme,
- Jan Krivanek,
- Jeremy Dasen,
- Claus Oxvig,
- Anders Nykjaer
Affiliations
- Pernille Bogetofte Thomasen
- 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
- Alena Salasova
- 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; Corresponding author
- Kasper Kjaer-Sorensen
- Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark
- Lucie Woloszczuková
- 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
- Josef Lavický
- Department of Histology and Embryology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic
- Hande Login
- 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
- Jeppe Tranberg-Jensen
- 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
- Sergio Almeida
- 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
- Sander Beel
- Department of Neurology and Department of Neurosciences, KU Leuven and Center for Brain & Disease Research VIB, 3000 Leuven, Belgium
- Michaela Kavková
- Department of Histology and Embryology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic
- Per Qvist
- Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark
- Mads Kjolby
- 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
- Peter Lund Ovesen
- 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
- Stella Nolte
- 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
- Benedicte Vestergaard
- 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
- Andreea-Cornelia Udrea
- 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
- Lene Niemann Nejsum
- Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark
- Moses V. Chao
- Department of Neuroscience and Physiology, NYU Langone Health, New York, NY 10016, USA
- Philip Van Damme
- Department of Neurology and Department of Neurosciences, KU Leuven and Center for Brain & Disease Research VIB, 3000 Leuven, Belgium
- Jan Krivanek
- Department of Histology and Embryology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic
- Jeremy Dasen
- Department of Neuroscience and Physiology, NYU Langone Health, New York, NY 10016, USA
- Claus Oxvig
- Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark
- Anders Nykjaer
- 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; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 11
p. 113333
Abstract
Summary: 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.
