SEMA4A

SEMA4A (also known as Semaphorin 4A, M-semaF, Sema4, CD100) is a protein encoded by the SEMA4A gene in humans. It belongs to the semaphorin family, a large group of secreted and transmembrane proteins known for their roles in axon guidance, immune responses, and angiogenesis.

Function:

SEMA4A functions as a signaling molecule involved in a variety of biological processes. Its primary functions include:

• Axon Guidance: Initially discovered for its role in guiding neuronal growth cones during development, SEMA4A helps neurons find their correct targets.
• Immune Regulation: SEMA4A plays a crucial role in regulating immune cell interactions and activation. It is expressed on various immune cells, including T cells, B cells, dendritic cells, and macrophages. It can act as a co-stimulatory molecule for T cell activation and can modulate the function of other immune cells.
• Angiogenesis: SEMA4A influences the formation of new blood vessels, a process known as angiogenesis. This is important in development, wound healing, and tumor growth.
• Bone Remodeling: SEMA4A has been implicated in the regulation of bone remodeling processes.

Mechanism of Action:

SEMA4A can function as both a receptor and a ligand, interacting with different receptors on target cells. Its main receptors include:

• Plexin B1: A transmembrane receptor that mediates many of SEMA4A's axon guidance functions.
• CD72: An inhibitory B cell receptor that modulates B cell activation and tolerance.
• TIM-2 (T cell immunoglobulin and mucin domain-containing protein 2): An immune checkpoint receptor involved in regulating T cell responses.

The interaction of SEMA4A with its receptors triggers intracellular signaling cascades that lead to changes in cell behavior, such as changes in cell motility, adhesion, and gene expression.

Clinical Significance:

Dysregulation of SEMA4A expression and signaling has been implicated in several diseases, including:

• Cancer: SEMA4A is often upregulated in various cancers, where it can promote tumor growth, angiogenesis, and metastasis.
• Autoimmune Diseases: Aberrant SEMA4A expression and signaling can contribute to the development and progression of autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis.
• Neurological Disorders: SEMA4A dysfunction may contribute to the pathogenesis of certain neurological disorders.

Structure:

The SEMA4A protein is a transmembrane protein with a large extracellular domain containing a sema domain, a PSI domain, and an Ig domain. These domains are important for receptor binding and protein-protein interactions. It also possesses a transmembrane domain and a cytoplasmic tail that mediates intracellular signaling.

Further Research:

Ongoing research is focused on further elucidating the precise roles of SEMA4A in various biological processes and diseases. Understanding the complexities of SEMA4A signaling pathways may lead to the development of novel therapeutic strategies for cancer, autoimmune diseases, and other disorders.