The NOTCH3 gene provides instructions for producing the Notch3 receptor protein. This receptor protein is located on the surface of the muscle cells that surround blood vessels (vascular smooth muscle cells). The Notch3 receptor protein is specific to arteries, which are blood vessels that carry blood from the heart to the rest of the body. The protein is not present in veins, which return blood to the heart. When certain molecules attach (bind) to Notch3 receptors, the receptors send signals to the nucleus of the cell. These signals then turn on (activate) particular genes within vascular smooth muscle cells. Notch3 receptors play a key role in the function and survival of vascular smooth muscle cells. These receptors are thought to be essential for the maintenance of healthy muscle cells in the brain's arteries.
More than 150 mutations in the NOTCH3 gene have been found to cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, commonly known as CADASIL. Almost all of these mutations change a single protein building block (amino acid) in the Notch3 receptor. The amino acid involved in most mutations is cysteine. The addition or deletion of a cysteine molecule in a certain area of the Notch3 receptor, known as the EGF-like domain, presumably affects Notch3 receptor function in vascular smooth muscle cells. Disruption of Notch3 functioning can lead to the self-destruction (apoptosis) of these cells. Damage to vascular smooth muscle cells is thought to cause recurrent strokes and other signs and symptoms of CADASIL.
- Neurogenic locus notch homolog protein 3
- Notch homolog 3
- Notch homolog 3 (Drosophila)