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Cadherins Interact With Synaptic Organizers to Promote Synaptic Differentiation
Masahito Yamagata1, Xin Duan1, Joshua R Sanes1
1Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, United States.
Frontiers in Molecular Neuroscience
|May 16, 2018
Summary
Classical cadherins, like N-cadherin (Cdh2), are crucial for neural development and synapse formation. This study shows Cdh2 and other cadherins promote neurite branching and synaptic differentiation by interacting with synaptic organizers.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Classical cadherins are key regulators of neural development, including synapse formation and remodeling.
- Studying N-cadherin (Cdh2) function is complicated by its endogenous expression in common cell lines.
Purpose of the Study:
- To investigate the role of N-cadherin (Cdh2) in neural development and synapse formation using a Cdh2-deficient cell line.
- To determine how Cdh2 interacts with synaptic organizers to promote neurite branching and synaptic differentiation.
Main Methods:
- CRISPR-mediated gene editing to create Cdh2-deficient HEK293 cells.
- Co-culture of rodent neurons with parental, Cdh2-mutant, and Cdh2-rescued HEK293 cells.
- Assays for neurite branching, presynaptic differentiation (synaptic vesicle clustering), and postsynaptic differentiation.
Main Results:
- Cdh2 promotes neurite branching.
- Cdh2 is essential for synaptic organizers (NLGL1, LRRtm2, Cadm1/SynCAM) to induce presynaptic differentiation.
- Cdh2 is required for Neurexin1β to promote postsynaptic differentiation.
- Other cadherins (Cdh4, Cdh6) can substitute for Cdh2.
- Cadherin function depends on homophilic interactions.
Conclusions:
- Classical cadherins, including Cdh2, work with synaptic organizers to promote synaptic differentiation.
- Cadherins may enhance synaptic differentiation by strengthening intracellular adhesion for organizer function.
- Cadherins facilitate high-affinity interactions necessary for synaptic differentiation.
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