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Molecular Mechanisms of L1 and NCAM Adhesion Molecules in Synaptic Pruning, Plasticity, and Stabilization

Bryce W Duncan1, Kelsey E Murphy1, Patricia F Maness1

  • 1Department of Biochemistry and Biophysics, Neuroscience Research Center, Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, NC, United States.

Frontiers in Cell and Developmental Biology
|February 15, 2021
PubMed

Insights

Neural cell adhesion molecules (CAMs) like L1 and NCAM regulate brain development by controlling synapse formation and stability. This process is crucial for normal brain function and understanding developmental disorders.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Molecular Biology

Background:

  • Mammalian brain circuits require precise formation and remodeling of excitatory and inhibitory synapses during development.
  • Synaptic regulation involves a complex interplay of proteins, including immunoglobulin (Ig)-class cell adhesion molecules (CAMs), pre- and post-synaptic components, and the extracellular matrix.

Purpose of the Study:

  • To review the current understanding of how L1 and NCAM family CAMs mediate developmental synapse regulation.
  • To explore the roles of these CAMs in synapse formation, remodeling, and plasticity during critical developmental periods.

Main Methods:

  • Review of existing literature on neuronal CAMs, synaptic plasticity, and extracellular matrix interactions.
  • Analysis of the molecular mechanisms underlying synapse stabilization and pruning mediated by L1-CAMs and NCAM.

Main Results:

  • L1 and NCAM family CAMs orchestrate synapse formation and remodeling through receptor-ligand interactions.
  • Ankyrins interact with L1-CAMs to enhance synaptic stability.
  • Extracellular matrix components like chondroitin sulfates and hyaluronic acid, along with linker proteins, stabilize synaptic contacts and limit plasticity.

Conclusions:

  • Neuronal CAMs and their interactions with the extracellular matrix are critical for establishing and refining synaptic connections during development.
  • Dysregulation of neuronal adhesion signaling and synaptic targeting may contribute to neurodevelopmental disorders such as autism, schizophrenia, and intellectual disability.

Keywords:
ankyrincell adhesion moleculeperineuronal netsynapsesynaptic stabilization

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