Schwannomin

Schwannomin, also known as merlin, is the protein product of the NF2 gene and functions as a tumor suppressor in the nervous system. It belongs to the ERM (ezrin–radixin–moesin) family of cytoskeletal adaptor proteins and is expressed in Schwann cells, other glial cells, and cells lining the meninges. The NF2 gene maps to chromosome 22q12.2. Merlin is a relatively large cytoskeletal-associated protein with an N-terminal FERM-like domain that links the plasma membrane to the actin cytoskeleton and to various signaling partners.

Function and mechanism: Merlin regulates cell proliferation and adhesion by modulating multiple signaling pathways, including the Hippo pathway. It acts as a scaffold that helps restrict mitogenic signaling at sites of cell–cell contact and membrane interfaces. Its activity is regulated by phosphorylation; phosphorylation at serine 518 by PAK1 and other kinases reduces activity, while dephosphorylation promotes membrane localization and tumor-suppressing function. Merlin also interacts with cytoskeletal components and membrane proteins to influence cell shape and motility.

Clinical significance: Inactivation of NF2—typically a germline mutation with a somatic second hit—causes neurofibromatosis type 2 (NF2). The disease is characterized by bilateral vestibular schwannomas and other intracranial tumors, such as meningiomas and ependymomas. Loss of merlin function disrupts contact inhibition and allows tumor development. Genetic testing for NF2 mutations supports diagnosis and family counseling. Management focuses on tumor monitoring and treatment, including microsurgery, radiosurgery, and emerging therapies that target related signaling pathways.

Merlin is named schwannomin for its abundance in Schwann cells, and the term is used interchangeably with merlin in modern references.

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