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Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
08:15

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Published on: October 17, 2014

Molecular modification of N-cadherin in response to synaptic activity.

H Tanaka1, W Shan, G R Phillips

  • 1Program in Cell Adhesion, The Mount Sinai School of Medicine, New York, New York 10029, USA.

Neuron
|March 9, 2000
PubMed
Summary

Synaptic adhesion, mediated by neural cadherin (N-cadherin), dynamically changes with neuronal activity. Activated N-cadherin dimerizes and resists proteases, indicating stable adhesion modulation during synaptic transmission.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Synaptic adhesion is crucial for neuronal function but its regulation remains unclear.
  • Neural cadherin (N-cadherin) is implicated in mediating adhesion between pre- and postsynaptic neurons at CNS synapses.

Purpose of the Study:

  • To investigate the dynamic changes in N-cadherin during synaptic activity.
  • To understand how synaptic activity influences cadherin-mediated adhesion.

Main Methods:

  • Hippocampal neurons in culture were depolarized using K+ treatment, NMDA, or alpha-latrotoxin.
  • Protease resistance assays were used to assess N-cadherin stability.
  • Immunocytochemistry was employed to visualize N-cadherin localization and dispersion.
  • Protein synthesis and internalization were evaluated.

Main Results:

  • Synaptic N-cadherin dimerized and acquired protease resistance upon neuronal depolarization, indicating enhanced adhesion.
  • These changes persisted for at least 2 hours post-stimulation.
  • N-cadherin dispersion was observed with K+ treatment, correlating with presynaptic membrane expansion, but not with NMDA application.
  • N-cadherin dimerization and protease resistance occurred independently of new protein synthesis or internalization.

Conclusions:

  • Synaptic adhesion is dynamically regulated by neuronal activity.
  • N-cadherin plays a key role in activity-dependent modulation of synaptic adhesion.
  • Different stimuli induce distinct N-cadherin responses, suggesting localized control mechanisms.