Revisión: Mecanismos moleculares de la neurofibromatosis tipo 2
Review: The molecular mechanisms of neurofibromatosis type 2
Resumen
En este trabajo presentamos una revisión sobre hallazgos más relevantes de la neurofibromatosis tipo 2 (NF2), la cual se conoce por ser un desorden autosómico dominante caracterizado por la presencia de schwannomas vestibulares bilaterales, aunque pueden presentarse otros tumores como meningiomas y ependimomas. Esta enfermedad es causada por diversas mutaciones en el gen NF2, mismo que codifica una proteína conocida como merlina o schwannomina. Merlina está relacionada estructuralmente con la familia de proteínas ERM (Ezrina-Radixina- Moesina), encargadas de acoplar las señales provenientes de las glucoproteínas de la membrana plasmática con el citoesqueleto de actina. El gen NF2 es considerado como un supresor de tumores, y las evidencias indican que merlina funciona regulando la proliferación y el crecimiento celular. Sin embargo, los mecanismos específicos por medio de los cuales merlina cumple con su función siguen siendo un enigma. Se han identificado diversas moléculas que interactúan con merlina, lo que ha proporcionado indicios acerca de los diversos procesos celulares en los cuales esta molécula participa. Entre las proteínas que interactúan con merlina se incluyen proteínas de función estructural, receptores de membrana plasmática, proteínas citosólicas, GTPasas y adaptadores citoesqueléticos. Las mutaciones en el gen NF2 afectan la funcionalidad de merlina, lo que produce alteraciones en los mecanismos de acción de merlina dando como origen a la NF2. Son necesarios más estudios para determinar con certeza el papel de merlina en el control de la proliferación celular.
Abstract
In this work, we present a review over the most relevant information of the neurofibromatosis type 2 (NF2), which is known as an autosomal dominant disorder characterized by the presence of bilateral vestibular schwannomas. Other tumors such as meningiomas and ependymomas may be present. The disease is caused by mutations in the NF2 gene, which encodes a protein known as merlin or schwannomin. Merlin is structurally related to the ERM (Ezrina-Radixina-Moesina) family of proteins, a group of molecules responsible for linking the signals coming from the plasma membrane glycoproteins to the actin cytoskeleton. The NF2 gene is considered as a tumor suppressor gene, and the evidence indicates that merlin functions by regulating the cell growth and proliferation. However, the specific mechanisms through which merlin fulfill its functions as a tumor suppressor remains enigmatic. Several molecules that interact with merlin have been identified. This has provided clues to determine the cellular processes in which merlin participates. These molecules include structural proteins, plasma membrane receptors, cytosolic proteins, GTPases, and cytoskeletal adapters. Mutations in the NF2 gene affect the functionality of merlin, altering tha mecanisms of action of merlin, giving rise to NF2. Further studies are needed to determine the precise role of merlin on the control of cell proliferation.
Keywords: neurofibromatosis type 2, merlin, cytoskeleton, plasma membrane.
Citas
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