Using the Neurofibromatosis Tumor Predisposition Syndromes to Understand Normal Nervous System Development
Merlin structure and function. (a) Merlin is a 595- (or 590-) amino-acid protein composed of three structural regions: an amino terminal domain (FERM), an α-helix domain, and a carboxyl terminal domain (CTD). There are two merlin isoforms. Isoform 1 contains exon 17 and lacks exon 16. Isoform 2 contains exon 16, which inserts 11 unique c-terminal amino acids followed by a termination codon that prevents the translation of exon 17. (b) Merlin forms an intramolecular complex in which the FERM domain associates with the CTD. Phosphorylation of merlin at Serine-518 results in an open conformation, which inactivates the tumor suppressor activity of merlin. (c) Merlin binds to the actin cytoskeleton, RTKs, and CD44 to form proper adherens junctions. It also inhibits RAC1 and YAP activity, which are important for normal growth regulation.