Roundabout signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by a SLIT protein binding to a Roundabout (ROBO) family receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:BHF, GOC:signaling]

The Roundabout (Robo) signaling pathway plays a critical role in axon guidance, cell migration, and tissue development. It is a highly conserved pathway across various species, including humans, flies, and worms. The pathway is primarily mediated by the interaction of Robo receptors with Slit ligands, which are secreted proteins.

Here's a detailed breakdown of the biological process:

1. **Ligand Binding:** Slit proteins, secreted from neighboring cells or tissues, act as ligands for Robo receptors. These ligands are characterized by their unique domain structure, which includes a conserved "Slit" domain responsible for binding to Robo receptors.

2. **Robo Receptor Activation:** Upon binding of Slit, Robo receptors undergo conformational changes, triggering downstream signaling events. Robo receptors are transmembrane proteins with a large extracellular domain containing multiple Ig-like repeats and a cytoplasmic domain.

3. **Downstream Signaling Cascades:** The activated Robo receptor interacts with intracellular adaptor proteins, such as Enabled (Ena), Dock180, and Trio, leading to the activation of Rho GTPases. These GTPases, particularly Rac1, play a crucial role in regulating cytoskeletal dynamics, cell adhesion, and migration.

4. **Axon Guidance and Cell Migration:** The activation of Rac1 promotes the assembly of F-actin, a key component of the cytoskeleton. This leads to the formation of lamellipodia and filopodia, which are protrusions essential for axonal growth and cell migration.

5. **Regulation of Cell Adhesion and Proliferation:** Robo signaling also influences cell adhesion and proliferation. Robo receptors can interact with cell adhesion molecules, such as integrins, modulating their function. Furthermore, Robo signaling can influence cell cycle regulation and promote cell survival.

6. **Tissue Development and Organogenesis:** The Roundabout signaling pathway is crucial for the proper development of various tissues and organs. For example, it plays a role in the formation of the nervous system, vascular system, and immune system.

7. **Disease Relevance:** Dysregulation of Robo signaling has been implicated in several human diseases, including cancer, neurological disorders, and immune system dysfunction.'
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Proteins (1)

Compounds (1)