Sema4A induces cell morphological changes through B-type plexin-mediated signaling.

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Semaphorins are crucial axonal guidance molecules.
• Sema4A, a class 4 semaphorin, is known to induce growth cone collapse in hippocampal neurons.
• Identifying Sema4A receptors and downstream signaling is key to understanding neural development.

Purpose of the Study:

• To identify the functional receptor for Sema4A on hippocampal neurons.
• To elucidate the intracellular signaling pathway mediating Sema4A-induced growth cone collapse.
• To determine the role of R-Ras in Sema4A signaling.

Main Methods:

• COS-7 cell transfection and contraction assays to identify Sema4A receptors and signaling components.
• Co-transfection of plexins and Rnd1 to assess signal transduction.
• Stimulation of primary mouse hippocampal neurons with Sema4A after transfection with a constitutively active R-Ras mutant.

Main Results:

• Sema4A binds to axonal guidance receptors Plexin-B1, -B2, and -B3.
• Co-expression of Rnd1 with B-type plexins in COS-7 cells induced Sema4A-triggered cell contraction.
• Expression of a constitutively active R-Ras mutant blocked Sema4A-induced growth cone collapse in hippocampal neurons.

Conclusions:

• B-type plexins act as functional Sema4A receptors, transmitting signals via Rnd1.
• Sema4A induces hippocampal growth cone collapse through the down-regulation of R-Ras activity.