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Published on: May 17, 2017
Ephrin-B1 and ephrin-B2 mediate EphB-dependent presynaptic development via syntenin-1
Andrew C McClelland1, Sean I Sheffler-Collins, Matthew S Kayser
1Department of Neuroscience, University of Pennsylvania School of Medicine, 1114 BRBII/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
Insights
Ephrin-B1 and Ephrin-B2 are crucial for presynaptic development, working with EphB and syntenin-1 to form synapses. Their coordinated action ensures proper presynaptic specialization in the central nervous system.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Synapse development requires presynaptic and postsynaptic coordination.
- EphB receptors regulate postsynaptic development but their role in presynaptic formation is unclear.
Purpose of the Study:
- To investigate the role of ephrin-B ligands and syntenin-1 in EphB-mediated presynaptic development.
Main Methods:
- Knockdown of ephrin-B1, ephrin-B2, ephrin-B3, and syntenin-1 in presynaptic components.
- Analysis of synaptic marker colocalization and synaptic specialization formation.
Main Results:
- Knockdown of ephrin-B1, ephrin-B2, or syntenin-1 impaired EphB-dependent presynaptic development.
- Ephrin-B1, ephrin-B2, and syntenin-1 form presynaptic clusters.
- Ephrin-B1 and ephrin-B2 act independently in synapse formation but cooperatively recruit syntenin-1.
Conclusions:
- Ephrin-B1 and ephrin-B2, along with syntenin-1, are essential mediators of presynaptic development in conjunction with EphB signaling.
Abstract:
The development of central nervous system synapses requires precise coordination between presynaptic and postsynaptic components. The EphB family controls postsynaptic development by interacting with glutamate receptors and regulating dendritic filopodia motility, but how EphBs induce the formation of presynaptic specializations is less well understood. Here, we show that knockdown of presynaptic ephrin-B1, ephrin-B2, or syntenin-1, but not ephrin-B3, prevents EphB-dependent presynaptic development. Ephrin-B1, ephrin-B2, and syntenin-1 are clustered together with presynaptic markers, suggesting that these molecules function jointly in presynaptic development. Knockdown of ephrin-B1 or ephrin-B2 reduces the number of synaptic specializations and the colocalization of syntenin-1 with synaptic markers. Simultaneous knockdown of ephrin-B1 and ephrin-B2 suggests that they function independently in the formation of synaptic contacts, but act together to recruit syntenin-1 to presynaptic terminals. Taken together, these results demonstrate that ephrin-B1 and ephrin-B2 function with EphB to mediate presynaptic development via syntenin-1.
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