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

Cristina Fernandez-Valle, Yong Tang, Jerome Ricard, Alma Rodenas-Ruano, Anna Taylor, Elizabeth Hackler, John Biggerstaff, Jared Iacovelli

Research output: Contribution to journalArticle

109 Citations (Scopus)

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 β1 integrin and erbB2. It defines a pathogenic mechanism for the development of NF2 in humans with mutations in exon 2 of NF2.

Original languageEnglish (US)
Pages (from-to)354-362
Number of pages9
JournalNature Genetics
Volume31
Issue number4
DOIs
StatePublished - Aug 1 2002
Externally publishedYes

Fingerprint

Neurofibromin 2
Paxillin
Exons
Mutation
Neurilemmoma
Neurofibromatosis 2
Schwann Cells
Missense Mutation
Growth
Integrins
Nervous System
Genes
Cell Membrane
Membranes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Fernandez-Valle, C., Tang, Y., Ricard, J., Rodenas-Ruano, A., Taylor, A., Hackler, E., ... Iacovelli, J. (2002). Paxillin binds schwannomin and regulates its density-dependent localization and effect on cell morphology. Nature Genetics, 31(4), 354-362. https://doi.org/10.1038/ng930

Paxillin binds schwannomin and regulates its density-dependent localization and effect on cell morphology. / Fernandez-Valle, Cristina; Tang, Yong; Ricard, Jerome; Rodenas-Ruano, Alma; Taylor, Anna; Hackler, Elizabeth; Biggerstaff, John; Iacovelli, Jared.

In: Nature Genetics, Vol. 31, No. 4, 01.08.2002, p. 354-362.

Research output: Contribution to journalArticle

Fernandez-Valle, C, Tang, Y, Ricard, J, Rodenas-Ruano, A, Taylor, A, Hackler, E, Biggerstaff, J & Iacovelli, J 2002, 'Paxillin binds schwannomin and regulates its density-dependent localization and effect on cell morphology', Nature Genetics, vol. 31, no. 4, pp. 354-362. https://doi.org/10.1038/ng930
Fernandez-Valle C, Tang Y, Ricard J, Rodenas-Ruano A, Taylor A, Hackler E et al. Paxillin binds schwannomin and regulates its density-dependent localization and effect on cell morphology. Nature Genetics. 2002 Aug 1;31(4):354-362. https://doi.org/10.1038/ng930
Fernandez-Valle, Cristina ; Tang, Yong ; Ricard, Jerome ; Rodenas-Ruano, Alma ; Taylor, Anna ; Hackler, Elizabeth ; Biggerstaff, John ; Iacovelli, Jared. / Paxillin binds schwannomin and regulates its density-dependent localization and effect on cell morphology. In: Nature Genetics. 2002 ; Vol. 31, No. 4. pp. 354-362.
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