XB-ART-8511
Neurochem Res
June 1, 2001;
26
(6):
703-12.
Rapid functional analysis in Xenopus oocytes of Po protein adhesive interactions.
Yoshida M
,
Colma DR
.
Abstract
We have developed a coupled Xenopus
oocyte expression system for evaluating the functional effects of mutations in known or suspected adhesion molecules, which allows for a very rapid assessment of intercellular adhesion. As a model protein, we first used Protein zero (Po), an adhesion molecule that mediates self-adhesion of the Schwann cell
plasma membrane to form compact myelin in the mammalian
PNS. A wide variety of mutations in Po cause certain human peripheral neuropathies, such as the Charcot-Marie-
Tooth disease (CMT) type 1B and Dejerine-Sottas syndrome (
DSS). After wild-type Po mRNA is injected, the protein is synthesized and correctly targeted to the
oocyte cell surface. When two oocytes are paired, wild-type Po redistributes and concentrates at the cell-cell apposition region, and by electron microscopy, the
oocyte pairs show close cell-cell appositions and are devoid of the microvilli that are observed in uninjected
oocyte pairs. These are hallmark features of highly adhesive cell:cell interfaces. Several point mutations in Po were engineered, corresponding to the molecular defects in the CMT type 1B or
DSS. The proteins encoded by these mutations reached the cell surface but failed to concentrate at the
oocyte interface. Po carrying a point mutation that is found in
DSS is not targeted on the
plasma membrane and fail to accumulate at the cell-cell contact site.
PubMed ID:
11519730
Article link:
Neurochem Res
Grant support:
[+]
Species referenced:
Xenopus laevis
Genes referenced:
egr2
mpz
pmp22
prx
GO keywords:
apical junction complex
[+]
Disease Ontology terms:
Charcot-Marie-Tooth disease type 1B
OMIMs:
CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 1B; CMT1B
[+]
References [+] :
Brackenbury,
Adhesion among neural cells of the chick embryo. I. An immunological assay for molecules involved in cell-cell binding.
1977,
Pubmed
Brackenbury,
Adhesion among neural cells of the chick embryo. I. An immunological assay for molecules involved in cell-cell binding.
1977,
Pubmed
D'Urso,
Protein zero of peripheral nerve myelin: biosynthesis, membrane insertion, and evidence for homotypic interaction.
1990,
Pubmed
Dahl,
Expression of functional cell-cell channels from cloned rat liver gap junction complementary DNA.
1987,
Pubmed
,
Xenbase
Doyle,
Protein zero, a nervous system adhesion molecule, triggers epithelial reversion in host carcinoma cells.
1995,
Pubmed
Doyle,
Glial-neuron interactions and the regulation of myelin formation.
1993,
Pubmed
Dumont,
Oogenesis in Xenopus laevis (Daudin). I. Stages of oocyte development in laboratory maintained animals.
1972,
Pubmed
,
Xenbase
Filbin,
Role of myelin P0 protein as a homophilic adhesion molecule.
1990,
Pubmed
Gao,
Acylation of myelin Po protein is required for adhesion.
2000,
Pubmed
Giese,
Mouse P0 gene disruption leads to hypomyelination, abnormal expression of recognition molecules, and degeneration of myelin and axons.
1992,
Pubmed
Hayasaka,
Charcot-Marie-Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene.
1993,
Pubmed
Hayasaka,
Mutation of the myelin P0 gene in Charcot-Marie-tooth neuropathy type 1.
1993,
Pubmed
Hayasaka,
De novo mutation of the myelin P0 gene in Dejerine-Sottas disease (hereditary motor and sensory neuropathy type III).
1994,
Pubmed
Kulkens,
Deletion of the serine 34 codon from the major peripheral myelin protein P0 gene in Charcot-Marie-Tooth disease type 1B.
1993,
Pubmed
Lai,
Two forms of 1B236/myelin-associated glycoprotein, a cell adhesion molecule for postnatal neural development, are produced by alternative splicing.
1987,
Pubmed
Lemke,
Isolation and sequence of a cDNA encoding the major structural protein of peripheral myelin.
1985,
Pubmed
Lemke,
Isolation and analysis of the gene encoding peripheral myelin protein zero.
1990,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Mishina,
Expression of functional acetylcholine receptor from cloned cDNAs.
1984,
Pubmed
,
Xenbase
Münchberg,
A paired oocyte adhesion assay reveals the homophilic binding properties of the Xenopus maternal cadherins, XB/U- and EP-cadherin.
1997,
Pubmed
,
Xenbase
Nagafuchi,
Cell binding function of E-cadherin is regulated by the cytoplasmic domain.
1989,
Pubmed
Nelis,
Rapid screening of myelin genes in CMT1 patients by SSCP analysis: identification of new mutations and polymorphisms in the P0 gene.
1995,
Pubmed
Paul,
Connexin46, a novel lens gap junction protein, induces voltage-gated currents in nonjunctional plasma membrane of Xenopus oocytes.
1991,
Pubmed
,
Xenbase
Schneider-Schaulies,
Recombinant peripheral myelin protein P0 confers both adhesion and neurite outgrowth-promoting properties.
1991,
Pubmed
Shapiro,
Crystal structure of the extracellular domain from P0, the major structural protein of peripheral nerve myelin.
1996,
Pubmed
Swenson,
Formation of gap junctions by expression of connexins in Xenopus oocyte pairs.
1989,
Pubmed
,
Xenbase
Warner,
Clinical phenotypes of different MPZ (P0) mutations may include Charcot-Marie-Tooth type 1B, Dejerine-Sottas, and congenital hypomyelination.
1996,
Pubmed
Werner,
Translation and functional expression of cell-cell channel mRNA in Xenopus oocytes.
1986,
Pubmed
,
Xenbase
Zhang,
Formation of a disulfide bond in the immunoglobulin domain of the myelin P0 protein is essential for its adhesion.
1994,
Pubmed
Zhang,
Myelin Po protein mutated at Cys21 has a dominant-negative effect on adhesion of wild type Po.
1998,
Pubmed
