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 KrivanekJeremy Dasen, Claus Oxvig, Anders Nykjaer*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number113333
JournalCell Reports
Volume42
Issue11
Number of pages34
ISSN2211-1247
DOIs
Publication statusPublished - Nov 2023

Keywords

  • CP: Developmental biology
  • CP: Neuroscience
  • SorCS2
  • VPS10p-D receptors
  • image segmentation
  • light-sheet microscopy
  • motor neurons
  • nerve injury
  • neurodevelopment
  • neurotrophic signaling
  • progranulin
  • zebrafish
  • Zebrafish/metabolism
  • Progranulins
  • Intercellular Signaling Peptides and Proteins
  • Granulins
  • Motor Neurons/metabolism
  • Mice, Knockout
  • Animals
  • Nerve Tissue Proteins/metabolism
  • Receptors, Cell Surface/metabolism
  • Mice

Fingerprint

Dive into the research topics of 'SorCS2 binds progranulin to regulate motor neuron development'. Together they form a unique fingerprint.

Cite this