Transsynaptic N-Cadherin Adhesion Complexes Control Presynaptic Vesicle and Bulk Endocytosis at Physiological...

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Transsynaptic adhesion complexes modulate mammalian glutamatergic synaptic transmission.
• Physiological regulation of synaptic vesicle endocytosis by adhesion molecules remains unclear.
• N-cadherin is localized near the peri-active zone, where temperature-dependent endocytosis occurs.

Purpose of the Study:

• To investigate the role of N-cadherin in synaptic vesicle endocytosis at near physiological temperatures.
• To determine if N-cadherin modulates different modes of endocytosis, including bulk endocytosis.
• To explore the mechanism underlying N-cadherin's modulation of endocytosis.

Main Methods:

• Synaptophysin-pHluorin imaging to monitor vesicle endocytosis.
• Analysis of N-cadherin expression and function.
• Super-resolution imaging to observe N-cadherin recruitment.
• Assessment of actin polymerization effects on endocytosis.

Main Results:

• N-cadherin expression and function were critical for various endocytosis modes, including bulk endocytosis.
• Actin polymerization partially rescued endocytosis defects in N-cadherin knockout models.
• Massive vesicle release induced strong N-cadherin recruitment to glutamatergic synapses.

Conclusions:

• N-cadherin plays a significant modulatory role in synaptic vesicle endocytosis at mammalian glutamatergic synapses.
• N-cadherin's effect on endocytosis may involve actin filament regulation.
• Adhesion protein-mediated coupling of exocytosis and endocytosis is a novel mechanism for synapse homeostasis.