Proteomics

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Proteomic analysis of the NF2/Merlin Interactome by Proximity Biotinylation

ABSTRACT: Neurofibromatosis type 2 is an inherited neoplastic disease consisting of schwannomas, meningiomas, and ependymomas that is caused by inactivation of the tumor suppressor gene NF2. The NF2 gene product, merlin, has no intrinsic catalytic activity; its tumor suppressor function is mediated through the proteins with which it interacts. However, there is no consensus about which merlin interactions are necessary for tumor suppression. We used proximity biotinylation followed by mass spectrometry and direct binding assays to characterize the proteins that associate with merlin and merlin mutants in immortalized Schwann cells. We identified 52 proteins that associate with merlin, including a previously unreported merlin binding protein, ASPP2. Our results identify merlin as a component of mechanosensing signal transduction pathways in cell junctions, in the context of a specific set of structures and molecules through which it acts, in a cell type relevant to schwannoma formation.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Robert Hennigan  

LAB HEAD: Nancy Ratner

PROVIDER: PXD012017 | Pride | 2019-04-25

REPOSITORIES: pride

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Proximity biotinylation identifies a set of conformation-specific interactions between Merlin and cell junction proteins.

Hennigan Robert F RF   Fletcher Jonathan S JS   Guard Steven S   Ratner Nancy N  

Science signaling 20190423 578

Neurofibromatosis type 2 is an inherited, neoplastic disease associated with schwannomas, meningiomas, and ependymomas and that is caused by inactivation of the tumor suppressor gene <i>NF2</i> The <i>NF2</i> gene product, Merlin, has no intrinsic catalytic activity; its tumor suppressor function is mediated through the proteins with which it interacts. We used proximity biotinylation followed by mass spectrometry and direct binding assays to identify proteins that associated with wild-type and  ...[more]

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