Title

Paxillin binds schwannomin and regulates its density-dependent localization and effect on cell morphology

Authors

Authors

C. Fernandez-Valle; Y. Tang; J. Ricard; A. Rodenas-Ruano; A. Taylor; E. Hackler; J. Biggerstaff;J. Iacovelli

Abbreviated Journal Title

Nature Genet.

Keywords

NEUROFIBROMATOSIS-2 TUMOR-SUPPRESSOR; GENE-PRODUCT; POINT MUTATIONS; TYPE-2 PROTEIN; LIM DOMAINS; LD4 MOTIF; KINASE; MERLIN; EZRIN; EXPRESSION; Genetics & Heredity

Abstract

Neurofibromatosis type 2 is an autosomal dominant disorder characterized by tumors, predominantly schwannomas, in the nervous system. It is caused by mutations in the gene NF2, encoding the growth regulator schwannomin (also known as merlin). Mutations occur throughout the 17-exon gene, with most resulting in protein truncation and undetectable amounts of schwannomin protein. Pathogenic mutations that result in production of defective schwannomin include in-frame deletions of exon 2 and three independent missense mutations within this same exon. Mice with conditional deletion of exon 2 in Schwann cells develop schwannomas, which confirms the crucial nature of exon 2 for growth control. Here we report that the molecular adaptor paxillin binds directly to schwannomin at residues 50-70, which are encoded by exon 2. This interaction mediates the membrane localization of schwannomin to the plasma membrane, where it associates with beta1 integrin and erbB2. It defines a pathogenic mechanism for the development of NF2 in humans with mutations in exon 2 of NF2.

Journal Title

Nature Genetics

Volume

31

Issue/Number

4

Publication Date

1-1-2002

Document Type

Article

Language

English

First Page

354

Last Page

362

WOS Identifier

WOS:000177147100009

ISSN

1061-4036

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