SEMA3 - semaphorin 3 | Elisa - Clia - Antibody - Protein

Background

Semaphorin 3 (SEMA3) is a member of the semaphorin family, a large group of proteins that play crucial roles in axonal guidance, cell migration, and immune responses. Semaphorins were initially identified as axon guidance cues in neural development, but their functions extend far beyond the nervous system. SEMA3 proteins are secreted and transmembrane proteins characterized by a conserved sema domain and are known to interact with neuropilins (NRPs) and plexins as their receptors. The semaphorin family is divided into eight classes, with classes 3 to 7 present in vertebrates, and SEMA3 belongs to class 3.

Protein Structure

SEMA3 proteins are secreted glycoproteins that share several common structural features:

• Sema Domain: The sema domain is a conserved 500-amino acid domain responsible for mediating protein-protein interactions. This domain is critical for the binding of SEMA3 to its receptors.
• Basic Domain: Following the sema domain, SEMA3 proteins typically have a basic domain that contributes to their functional properties.
• Immunoglobulin (Ig)-like Domain: Some SEMA3 proteins contain Ig-like domains, which are involved in receptor interactions.
• Polybasic C-Terminus: The C-terminal region of SEMA3 is often rich in basic residues, which can bind to cell surface receptors and extracellular matrix components.

SEMA3 proteins interact with their receptors through these structural motifs, facilitating their role in signaling pathways that control cell behavior.

Classification and Subtypes

The semaphorin family is divided into eight classes based on structural and functional characteristics. SEMA3 belongs to class 3, which includes several members:

1. SEMA3A: Known for its role in neural development and immune response modulation.
2. SEMA3B: Involved in tumor suppression and neural guidance.
3. SEMA3C: Plays roles in cardiovascular development and cancer.
4. SEMA3D: Functions in neural development and immune regulation.
5. SEMA3E: Known for its anti-angiogenic properties and roles in immune responses.
6. SEMA3F: Implicated in neural development and tumor suppression.
7. SEMA3G: Less well-characterized but involved in similar signaling pathways as other SEMA3 proteins.

Function and Biological Significance

SEMA3 proteins are multifunctional and participate in various biological processes:

1. Axonal Guidance: In the nervous system, SEMA3 proteins guide axons to their targets by repelling or attracting growth cones, thus shaping the neural network.
2. Cell Migration: SEMA3 proteins influence the migration of various cell types, including neurons, endothelial cells, and immune cells. This function is critical during development and in pathological conditions like cancer and inflammation.
3. Angiogenesis: Some SEMA3 members, such as SEMA3E, have anti-angiogenic properties, inhibiting the formation of new blood vessels, which is important in both physiological processes and disease states like cancer.
4. Tumor Suppression: SEMA3 proteins like SEMA3B and SEMA3F have been shown to suppress tumor growth and metastasis by inhibiting cancer cell migration and invasion.
5. Immune Regulation: SEMA3 proteins modulate immune cell function, influencing responses to infection and inflammation.

Clinical Issues

The dysregulation of SEMA3 signaling is associated with several pathological conditions:

• Cancer: Altered expression of SEMA3 proteins is observed in various cancers. For example, SEMA3A and SEMA3B act as tumor suppressors, and their downregulation is associated with increased tumor growth and metastasis. Therapeutic strategies targeting SEMA3 signaling are being explored to inhibit tumor progression.
• Neurological Disorders: Mutations or abnormal expression of SEMA3 genes can lead to neural developmental disorders, such as congenital mirror movements and Kallmann syndrome.
• Cardiovascular Diseases: SEMA3C and SEMA3E are involved in cardiovascular development, and their dysregulation can contribute to congenital heart defects and other cardiovascular conditions.
• Inflammation and Autoimmunity: SEMA3 proteins modulate immune responses, and their dysregulation can lead to chronic inflammatory conditions and autoimmune diseases.

Summary

SEMA3 proteins are critical regulators of cellular behavior, influencing processes like axonal guidance, cell migration, angiogenesis, and immune responses. They achieve these effects through interactions with receptors such as neuropilins and plexins. Dysregulation of SEMA3 signaling pathways is implicated in various diseases, including cancer, neurological disorders, cardiovascular diseases, and immune conditions. Understanding the roles of SEMA3 proteins in these processes provides insights into their potential as therapeutic targets in multiple disease contexts. As research continues, the therapeutic modulation of SEMA3 signaling holds promise for treating a range of pathological conditions.