The podosomal-adaptor protein SH3PXD2B is essential for normal postnatal development

Mao Mao; Daniel R Thedens; Bo Chang; Belinda S Harris; Qing Yin Zheng; Kenneth R Johnson; Leah Rae Donahue; Michael G Anderson

doi:10.1007/s00335-009-9210-9

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The podosomal-adaptor protein SH3PXD2B is essential for normal postnatal development

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The podosomal-adaptor protein SH3PXD2B is essential for normal postnatal development

Mao Mao, Daniel R Thedens, Bo Chang, Belinda S Harris, Qing Yin Zheng, Kenneth R Johnson, Leah Rae Donahue and Michael G Anderson

Mammalian genome, Vol.20(8), pp.462-475

08/2009

DOI: 10.1007/s00335-009-9210-9

PMCID: PMC2759419

PMID: 19669234

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Abstract

Podosome-type adhesions are actin based membrane protrusions involved in cell-matrix adhesion and extracellular matrix degradation. Despite growing knowledge of many proteins associated with podosome-type adhesions, much remains unknown concerning the function of podosomal proteins at the level of the whole animal. In this study, the spontaneous mouse mutant nee was used to identify a component of podosome-type adhesions that is essential for normal postnatal growth and development. Mice homozygous for the nee allele exhibited runted growth, craniofacial and skeletal abnormalities, ocular anterior segment dysgenesis, and hearing impairment. Adults also exhibited infertility and a form of lipodystrophy. Using genetic mapping and DNA sequencing, the cause of nee phenotypes was identified as a 1 bp deletion within the Sh3pxd2b gene on mouse Chromosome 11. Whereas the wild-type Sh3pxd2b gene is predicted to encode a protein with 1 PX domain and 4 SH3 domains, the nee mutation is predicted to cause a frameshift and a protein truncation altering a portion of the third SH3 domain and deleting all of the fourth SH3 domain. The SH3PXD2B protein is believed to be an important component of podosomes likely to mediate protein-protein interactions with membrane spanning metalloproteinases. Testing this directly, SH3PXD2B localized to podosomes in constitutively active Src transfected fibroblasts and through its last SH3 domain associated with a transmembrane member of a disintegrin and metalloproteinase family of proteins, ADAM15. These results identify SH3PXD2B as a podosomal-adaptor protein required for postnatal growth and development, particularly within physiologic contexts involving extracellular matrix regulation.

Details

Title: Subtitle: The podosomal-adaptor protein SH3PXD2B is essential for normal postnatal development
Creators: Mao Mao - Department of Molecular Physiology and Biophysics, The University of Iowa, Iowa City, Iowa 52242, USA
Daniel R Thedens - Department of Radiology, The University of Iowa, Iowa City, Iowa 52242, USA
Bo Chang - The Jackson Laboratory, Bar Harbor, Maine, 04609, USA
Belinda S Harris - The Jackson Laboratory, Bar Harbor, Maine, 04609, USA
Qing Yin Zheng - The Jackson Laboratory, Bar Harbor, Maine, 04609, USA
Kenneth R Johnson - The Jackson Laboratory, Bar Harbor, Maine, 04609, USA
Leah Rae Donahue - The Jackson Laboratory, Bar Harbor, Maine, 04609, USA
Michael G Anderson - Department of Molecular Physiology and Biophysics, The University of Iowa, Iowa City, Iowa 52242, USA
Resource Type: Journal article
Publication Details: Mammalian genome, Vol.20(8), pp.462-475
DOI: 10.1007/s00335-009-9210-9
PMID: 19669234
PMCID: PMC2759419
NLM abbreviation: Mamm Genome
ISSN: 0938-8990
eISSN: 1432-1777
Language: English
Date published: 08/2009
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Electrical and Computer Engineering; Molecular Physiology and Biophysics; Ophthalmology and Visual Sciences
Record Identifier: 9984025332402771

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