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Published on: December 21, 2011
The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras
Izumi Oinuma1, Yukio Ishikawa, Hironori Katoh
1Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Abstract:
Plexins are cell surface receptors for semaphorin molecules, and their interaction governs cell adhesion and migration in a variety of tissues. We report that the Semaphorin 4D (Sema4D) receptor Plexin-B1 directly stimulates the intrinsic guanosine triphosphatase (GTPase) activity of R-Ras, a member of the Ras superfamily of small GTP-binding proteins that has been implicated in promoting cell adhesion and neurite outgrowth. This activity required the interaction of Plexin-B1 with Rnd1, a small GTP-binding protein of the Rho family. Down-regulation of R-Ras activity by the Plexin-B1-Rnd1 complex was essential for the Sema4D-induced growth cone collapse in hippocampal neurons. Thus, Plexin-B1 mediates Sema4D-induced repulsive axon guidance signaling by acting as a GTPase activating protein for R-Ras.
Insights
Plexin-B1, a Semaphorin 4D receptor, activates R-Ras GTPase activity. This interaction is crucial for Semaphorin 4D-induced repulsive axon guidance signaling in neurons.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Plexins are cell surface receptors binding semaphorins, regulating cell adhesion and migration.
- Ras superfamily proteins, like R-Ras, are critical for cell adhesion and neurite outgrowth.
Purpose of the Study:
- To investigate the interaction between Plexin-B1 and R-Ras.
- To elucidate the role of Plexin-B1-R-Ras signaling in Semaphorin 4D-mediated neuronal guidance.
Main Methods:
- Investigated the direct interaction between Plexin-B1 and R-Ras.
- Examined the role of Rnd1 in Plexin-B1-R-Ras complex formation.
- Assessed the effect of this complex on R-Ras GTPase activity.
- Studied Sema4D-induced growth cone collapse in hippocampal neurons.
Main Results:
- Plexin-B1 directly stimulates the GTPase activity of R-Ras.
- This activation requires the interaction of Plexin-B1 with Rnd1.
- The Plexin-B1-Rnd1 complex down-regulates R-Ras activity.
- This down-regulation is essential for Sema4D-induced growth cone collapse.
Conclusions:
- Plexin-B1 acts as a GTPase activating protein for R-Ras.
- Plexin-B1 mediates Sema4D-induced repulsive axon guidance signaling via R-Ras regulation.
- This pathway is critical for neuronal development and guidance.
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