ADAM10

ADAM10 is a member of the ADAM family (A Disintegrin and Metalloproteinase), which are proteins involved in a variety of biological processes, including cell signaling, cell adhesion, and proteolysis. ADAM10 is known for its role in the shedding of membrane proteins, which is a critical process in cell communication and signal transduction.

Structure

ADAM10 is a transmembrane protein that consists of several distinct domains: a prodomain, a metalloprotease domain, a disintegrin domain, a cysteine-rich domain, an EGF-like domain, a transmembrane domain, and a cytoplasmic tail. The metalloprotease domain is responsible for its enzymatic activity, allowing it to cleave specific substrates at the cell surface.

Function

ADAM10 is involved in the proteolytic processing of several important substrates, including the Notch receptor, amyloid precursor protein (APP), and E-cadherin. This processing is crucial for the regulation of cell fate, neuronal development, and cell-cell adhesion.

Notch Signaling

In the Notch signaling pathway, ADAM10 acts as an _-secretase, cleaving the Notch receptor to release the Notch intracellular domain (NICD), which translocates to the nucleus to regulate gene expression. This process is essential for cell differentiation and developmental processes.

Alzheimer's Disease

ADAM10 is also implicated in the pathogenesis of Alzheimer's disease. It cleaves the amyloid precursor protein (APP) in a non-amyloidogenic pathway, preventing the formation of amyloid-beta peptides, which are associated with the development of amyloid plaques in the brain.

E-cadherin Shedding

ADAM10 mediates the shedding of E-cadherin, a protein critical for cell-cell adhesion in epithelial tissues. This shedding can influence cell migration, invasion, and tumor progression.

Regulation

The activity of ADAM10 is tightly regulated by its prodomain, which maintains the enzyme in an inactive state until it is cleaved. Additionally, ADAM10 activity can be modulated by phosphorylation, protein-protein interactions, and lipid rafts in the cell membrane.

Clinical Significance

Due to its involvement in critical cellular processes, ADAM10 is a potential target for therapeutic intervention in diseases such as cancer, Alzheimer's disease, and cardiovascular diseases. Inhibitors of ADAM10 are being explored for their potential to modulate its activity in these conditions.

Related pages

• ADAM family
• Notch signaling pathway
• Alzheimer's disease
• Cell adhesion