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Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors
T Takahashi1, A Fournier, F Nakamura
1Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Cell
|October 16, 1999
Summary
Semaphorin-3A (Sema3A) binding to axons involves a complex of neuropilin-1 (NP-1) and plexin-1 (Plex 1). This NP-1/Plex 1 complex, not NP-1 alone, mediates Sema3A
Area of Science:
- Neuroscience
- Cell Biology
Background:
- Class 1 and 3 semaphorins are axon guidance cues that mediate repulsion.
- These semaphorins bind to distinct cell surface proteins, suggesting complex receptor mechanisms.
Purpose of the Study:
- To investigate the interaction between plexin-1 (Plex 1) and neuropilin-1 (NP-1) in mediating semaphorin-3A (Sema3A) signaling.
- To determine the functional role of NP-1/Plex 1 complexes in Sema3A-induced cellular responses.
Main Methods:
- Co-immunoprecipitation to assess protein complex formation.
- Ligand binding assays to measure semaphorin affinity.
- Cell morphology assays using adherent cells.
- Dominant-negative approaches in sensory neurons.
- Confocal microscopy to visualize protein redistribution.
Main Results:
- Neuropilin-1 (NP-1) and plexin-1 (Plex 1) form a stable complex.
- The NP-1/Plex 1 complex exhibits higher affinity for semaphorin-3A (Sema3A) than NP-1 alone.
- Sema3A binding to NP-1/Plex 1 complexes induces cell rounding, unlike binding to NP-1 alone.
- Dominant-negative Plex 1 inhibits Sema3A-induced growth cone collapse.
- Sema3A treatment causes NP-1 and plexin to cluster in growth cones.
Conclusions:
- Physiologic semaphorin-3A (Sema3A) receptors are composed of neuropilin-1 (NP-1)/plexin-1 (Plex 1) complexes.
- This complex formation is crucial for Sema3A-mediated axon guidance and cellular responses.
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