Related Experiment Video

Updated: Apr 28, 2026

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
10:16

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry

Published on: January 6, 2017

7.2K

SorCS2 regulates dopaminergic wiring and is processed into an apoptotic two-chain receptor in peripheral glia

Simon Glerup1, Ditte Olsen2, Christian B Vaegter2

  • 1The Lundbeck Foundation Research Center MIND, Department of Biomedicine, Aarhus University, Vennelyst Boulevard 4, 8000 C Aarhus, Denmark; Danish Research Institute of Translational Neuroscience DANDRITE Nordic-EMBL Partnership, Department of Biomedicine, Aarhus University, Vennelyst Boulevard 4, 8000 C Aarhus, Denmark; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

Neuron
|June 9, 2014
PubMed

Insights

SorCS2 acts as a dual receptor for proneurotrophins (proNTs), influencing neuronal development and glial apoptosis. Its processing differs between CNS neurons and PNS glia, impacting dopamine systems and nerve injury responses.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Developmental Biology

Background:

  • Neuronal circuit development and regeneration rely on balancing trophic and apoptotic signals.
  • The role of SorCS2 in mediating these signals, particularly in response to proneurotrophins (proNTs), is not fully understood.

Purpose of the Study:

  • To identify SorCS2 as a proNT receptor and elucidate its distinct functions in central nervous system (CNS) neurons and peripheral nervous system (PNS) glia.
  • To investigate the impact of SorCS2 and p75(NTR) deficiency on neuronal development, dopamine metabolism, and behavior.

Main Methods:

  • Utilized knockout mouse models (SorCS2- and p75(NTR)-deficient) to study CNS and PNS functions.
  • Analyzed dopamine levels, metabolism, and dopaminergic innervation patterns.
  • Examined Schwann cell apoptosis following sciatic nerve injury.

Main Results:

  • Single-chain SorCS2 in CNS neurons mediates proBDNF-induced growth cone collapse and is crucial for normal dopamine levels and metabolism.
  • SorCS2 or p75(NTR) deficiency in mice leads to dopaminergic hyperinnervation and ADHD-like behavioral responses.
  • Two-chain SorCS2 in PNS glia mediates proNT-dependent Schwann cell apoptosis, which is attenuated in Sorcs2(-/-) mice after nerve injury.

Conclusions:

  • SorCS2 functions as a proNT receptor, mediating distinct trophic and apoptotic signals in CNS neurons and PNS glia.
  • Differential processing of SorCS2 into single-chain (neurons) and two-chain (glia) isoforms dictates cell-type-specific responses to proneurotrophins.
  • These findings reveal a novel mechanism for regulating neuronal circuit development, dopamine homeostasis, and glial cell fate during nerve injury.

More Related Videos

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons10:50

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Published on: April 24, 2021

1.1K
Morphological and Functional Evaluation of Axons and their Synapses during Axon Death in Drosophila melanogaster10:29

Morphological and Functional Evaluation of Axons and their Synapses during Axon Death in Drosophila melanogaster

Published on: March 16, 2020

8.0K

Related Concept Videos

The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.2K
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
6.1K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
64.6K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized...
3.9K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
15.2K