Synaptic cell adhesion molecule SynCAM 1 is a target for polysialylation in postnatal mouse brain

Area of Science:

• Neuroscience
• Glycobiology
• Molecular Biology

Background:

• Polysialic acid (polySia) is crucial for brain development and synaptic plasticity.
• Neural Cell Adhesion Molecule (NCAM) is the primary carrier of polySia in the nervous system.
• Previous studies observed polySia in NCAM-deficient mice, suggesting other carriers exist.

Purpose of the Study:

• To identify novel protein scaffolds for polysialic acid (polySia) beyond NCAM.
• To investigate the role of SynCAM 1 as a potential polySia carrier.
• To understand the functional implications of polySia on SynCAM 1 in neural development.

Main Methods:

• Glycoproteomics approach using affinity purification of polysialylated molecules.
• Peptide mass fingerprinting for protein identification.
• In vitro polysialylation assays using ST8SiaII and ST8SiaIV enzymes.
• Immunohistochemical analysis of brain sections.

Main Results:

• Synaptic Cell Adhesion Molecule 1 (SynCAM 1) was identified as a novel carrier of polySia.
• Polysialylated SynCAM 1 was found in both wild-type and NCAM-deficient perinatal mouse brains.
• PolySia is attached to N-glycans on the first Ig domain of SynCAM 1, inhibiting homophilic binding.
• PolySia-SynCAM 1 is exclusively expressed by NG2 cells in the developing brain.

Conclusions:

• SynCAM 1 is a significant carrier of polysialic acid in the vertebrate brain.
• PolySia modification of SynCAM 1 modulates its function, particularly homophilic binding.
• PolySia-SynCAM 1 on NG2 cells suggests a role in integrating glia into neural networks.
• This discovery opens new avenues for understanding neural development and glial function.