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PMID:16436605

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Citation

Amici, SA, Dunn, WA Jr, Murphy, AJ, Adams, NC, Gale, NW, Valenzuela, DM, Yancopoulos, GD and Notterpek, L (2006) Peripheral myelin protein 22 is in complex with alpha6beta4 integrin, and its absence alters the Schwann cell basal lamina. J. Neurosci. 26:1179-89

Abstract

Peripheral myelin protein 22 (PMP22) is a tetraspan membrane glycoprotein, the misexpression of which is associated with hereditary demyelinating neuropathies. Myelinating Schwann cells (SCs) produce the highest levels of PMP22, yet the function of the protein in peripheral nerve biology is unresolved. To investigate the potential roles of PMP22, we engineered a novel knock-out (-/-) mouse line by replacing the first two coding exons of pmp22 with the lacZ reporter. PMP22-deficient mice show strong beta-galactosidase reactivity in peripheral nerves, cartilage, intestines, and lungs, whereas phenotypically they display the characteristics of tomaculous neuropathy. In the absence of PMP22, myelination of peripheral nerves is delayed, and numerous axon-SC profiles show loose basal lamina, suggesting altered interactions of the glial cells with the extracellular matrix. The levels of beta4 integrin, a molecule involved in the linkage between SCs and the basal lamina, are severely reduced in nerves of PMP22-deficient mice. During early stages of myelination, PMP22 and beta4 integrin are coexpressed at the cell surface and can be coimmunoprecipitated together with laminin and alpha6 integrin. In agreement, in clone A colonic carcinoma cells, epitope-tagged PMP22 forms a complex with beta4 integrin. Together, these data indicate that PMP22 is a binding partner in the integrin/laminin complex and is involved in mediating the interaction of SCs with the extracellular environment.

Links

PubMed Online version:10.1523/JNEUROSCI.2618-05.2006

Keywords

Adenocarcinoma/chemistry; Adenocarcinoma/pathology; Animals; Basement Membrane/metabolism; Basement Membrane/ultrastructure; Binding Sites; Cell Line, Tumor/chemistry; Coculture Techniques; Colonic Neoplasms/chemistry; Colonic Neoplasms/pathology; Exons/genetics; Ganglia, Spinal/cytology; Humans; Integrin alpha6beta4/chemistry; Integrin alpha6beta4/metabolism; Lac Operon; Laminin/metabolism; Mice; Mice, Knockout; Mice, Transgenic; Multiprotein Complexes; Myelin Proteins/chemistry; Myelin Proteins/deficiency; Myelin Proteins/genetics; Myelin Proteins/metabolism; Myelin Proteins/physiology; Organ Specificity; Peripheral Nervous System Diseases/genetics; Peripheral Nervous System Diseases/metabolism; Peripheral Nervous System Diseases/pathology; Phenotype; Protein Binding; Protein Interaction Mapping; Rats; Schwann Cells/metabolism; Schwann Cells/ultrastructure; Sciatic Nerve/metabolism; Sciatic Nerve/ultrastructure

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:ITB4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P16646
PR:Q61739

F

Seeded From UniProt

complete

MOUSE:ITB4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:A2A863
PR:Q61739

F

Seeded From UniProt

complete

MOUSE:ITB4

located_in

GO:0009986: cell surface

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PMP22

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:A2A863
PR:Q61739

F

Seeded From UniProt

complete

MOUSE:PMP22

located_in

GO:0009986: cell surface

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ITA6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:A2A863
PR:P16646

F

Seeded From UniProt

complete

MOUSE:PMP22

acts_upstream_of_or_within

GO:0022011: myelination in peripheral nervous system

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3614822

P

Seeded From UniProt

complete

MOUSE:PMP22

acts_upstream_of_or_within

GO:0030913: paranodal junction assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3614822

P

Seeded From UniProt

complete

MOUSE:PMP22

acts_upstream_of_or_within

GO:0035264: multicellular organism growth

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3614822

P

Seeded From UniProt

complete

MOUSE:PMP22

part_of

GO:0043256: laminin complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PMP22

acts_upstream_of_or_within

GO:0051146: striated muscle cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3614822

P

Seeded From UniProt

complete

MOUSE:PMP22

acts_upstream_of_or_within

GO:0061744: motor behavior

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3614822

P

Seeded From UniProt

complete

MOUSE:PMP22

acts_upstream_of_or_within

GO:0071711: basement membrane organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3614822

P

Seeded From UniProt

complete

MOUSE:PMP22

acts_upstream_of_or_within

GO:0007422: peripheral nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3614822

P

Seeded From UniProt

complete

MOUSE:PMP22

acts_upstream_of_or_within

GO:0007618: mating

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3614822

P

Seeded From UniProt

complete

MOUSE:PMP22

part_of

GO:0008305: integrin complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PMP22

part_of

GO:0009986: cell surface

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PMP22

acts_upstream_of_or_within

GO:0010628: positive regulation of gene expression

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3614822

P

Seeded From UniProt

complete

Notes

See also

References

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