Structure-Guided Insights into the Function of Merlin in Neurofibromatosis 2 (NF2).

摘要

Neurofibromatosis type 2 (NF2) is caused by inherited or sporadic mutations in the NF2 gene, and NF2 patients are highly prone to developing bilateral vestibular schwannomas or meningiomas. NF2 encodes two alternatively spliced forms, merlin-1 and merlin-2, which differ at their C-termini. Merlin belongs to ERM (ezrin-radixin-moesin) family of proteins that localize to adhesion complexes, bind to cell surface receptors and the actin cytoskeleton and, accordingly, play important roles in organizing cortical membrane domains. Finally the functions of ERM family proteins are regulated by alterations in their conformation triggered by binding to their partners, phosphorylation by select kinases, and by binding of acidic phospholipids (Figure 1).