Peripheral myelin protein 22 is a constituent of intercellular junctions in epithelia

Notterpek, Lucia; Roux, Kyle J.; Amici, Stephanie A.; Yazdanpour, Amy; Rahner, Christoph; Fletcher, Brad S.

doi:10.1073/pnas.251548398

Cited by 91 publications

(101 citation statements)

References 46 publications

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“…The detection of ␤-gal in the aortic arch of the heart (Fig. 2 D) agrees with our findings on the expression of PMP22 in a variety of vascular tissue (Notterpek et al, 2001;Roux et al, 2004). Other non-neural tissues that show robust reporter expression include the lungs, intestines, and cartilage.…”

Section: Discussionsupporting

confidence: 89%

“…In agreement, certain mutations in PMP22 are associated with childhood-onset dysmyelinating neuropathies in humans (Roa et al, 1993;Garcia et al, 1998). The localization of PMP22 at cell-cell junctions of various epithelia and endothelia suggests a possible role in mediating myelin wrapping and intercellular adhesion (Notterpek et al, 2001;Roux et al, 2004Roux et al, , 2005. Overexpression of PMP22 in epithelial cells alters their migratory behavior and changes the functional properties of cell-cell contacts (Roux et al, 2005).…”

Section: Introductionmentioning

confidence: 73%

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Peripheral Myelin Protein 22 Is in Complex with α6β4 Integrin, and Its Absence Alters the Schwann Cell Basal Lamina

Amici¹,

Dunn²,

Murphy³

et al. 2006

J. Neurosci.

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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 (Ϫ/Ϫ) mouse line by replacing the first two coding exons of pmp22 with the lacZ reporter. PMP22-deficient mice show strong ␤-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 ␤4 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 ␤4 integrin are coexpressed at the cell surface and can be coimmunoprecipitated together with laminin and ␣6 integrin. In agreement, in clone A colonic carcinoma cells, epitope-tagged PMP22 forms a complex with ␤4 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.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 73%

Peripheral Myelin Protein 22 Is in Complex with α6β4 Integrin, and Its Absence Alters the Schwann Cell Basal Lamina

Amici¹,

Dunn²,

Murphy³

et al. 2006

J. Neurosci.

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“…3), suggesting that this network may be correlated with the colonic cell differentiation induced by SB. Indeed, PMP22 [29], RB1 [30], NDRG1 [31], IGF2R [32], IGF2 [33], JUNB [34], TIMP1 [35] and THRA [36] have been reported to be expressed in the small intestine or colon. This network includes IGF2 at its center.…”

Section: Discussionmentioning

confidence: 99%

Genetic networks responsive to sodium butyrate in colonic epithelial cells

et al. 2006

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We performed microarray and computational gene network analyses to identify the detailed mechanisms by which sodium butyrate (SB) induces cell growth arrest and the differentiation of mouse colonic epithelial MCE301 cells. Two thousand six hundred four differentially expressed probe sets were identified in the cells treated with 2 mM SB and were classified into four groups. Of these, the gradually increased group and the gradually and remarkably decreased group contained the genetic networks for cellular development and cell cycles or canonical pathways for fatty acid biosynthesis and pyrimidine metabolism, respectively. The present results provide a basis for understanding the detailed molecular mechanisms of action of SB in colonic epithelial cells.

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“…This pathway is known to be involved in modulating the actin cytoskeleton, cell polarity, adhesion, and migration (Donaldson, 2003). Together, these findings support the notion that PMP22 has a significant role in basic cellular processes, extending beyond an involvement in Schwann cell myelination.We previously described PMP22 as a constituent of apical intercellular junctions in epithelial and endothelial cells (Notterpek et al, 2001;Roux et al, 2004). Although PMP22 shares significant amino acid homology with members of the claudin superfamily, overexpression of the protein in L-fibroblasts (Notterpek et al, 2001) or C6 glioma cells (Takeda et al, 2001) did not induce tight junction strands.…”

mentioning

confidence: 99%

“…After plating MDCK I cells on filters (3 ϫ 10 5 cells/cm 2 ), the medium was replaced every 24 h until the sixth day when TER levels had reached a steady state. For the Ca 2ϩ -switch assay (Gumbiner and Simons, 1986), cells were treated with EDTA (4 mM) containing media for 4 h (Notterpek et al, 2001) or for 18 h in Ca 2ϩ -and Mg 2ϩ -free media with 5% Chelex (SigmaAldrich, St. Louis, MO)-treated FCS. …”

mentioning

confidence: 99%

Modulation of Epithelial Morphology, Monolayer Permeability, and Cell Migration by Growth Arrest Specific 3/Peripheral Myelin Protein 22

Roux

Amici

Fletcher

et al. 2005

MBoC

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Peripheral myelin protein 22 (PMP22) is associated with a subset of hereditary peripheral neuropathies. Although predominantly recognized as a transmembrane constituent of peripheral nerve myelin, PMP22 is localized to epithelial and endothelial cell-cell junctions, where its function remains unknown. In this report, we investigated the role of PMP22 in epithelial biology. Expression of human PMP22 (hPMP22) slows cell growth and induces a flattened morphology in Madin-Darby canine kidney (MDCK) cells. The transepithelial electrical resistance (TER) and paracellular flux of MDCK monolayers are elevated by hPMP22 expression. After calcium switch, peptides corresponding to the second, but not the first, extracellular loop of PMP22 perturb the recovery of TER and paracellular flux. Finally, subsequent to wounding, epithelial monolayers expressing hPMP22 fail to migrate normally. These results indicate that PMP22 is capable of modulating several aspects of epithelial cell biology, including junctional permeability and wound closure. INTRODUCTIONThe tetraspan glycoprotein peripheral myelin protein 22 (PMP22), also known as growth arrest specific 3 (gas3) gene, has proposed roles in peripheral nerve myelin formation, cell-cell interactions, and cell proliferation (Suter and Snipes, 1995). Although the highest expression levels are found in myelin-forming Schwann cells, PMP22 mRNA can be detected in a multitude of developing and mature nonneural tissues, including epithelia of the intestine (Baechner et al., 1995;Taylor et al., 1995;Wulf and Suter, 1999) and the choroid plexus (Roux et al., 2004). The specific role of PMP22 in Schwann cells remains undefined, although it is known that altered expression is associated with heritable demyelinating peripheral neuropathies (Naef and Suter, 1998). Similarly, the function of the protein at nonneural locations remains undetermined.In vitro studies have identified a role for PMP22 in the regulation of cell proliferation and morphology. In Schwann cells, elevated expression delays the transition from G0/G1 to the S phase of the cell cycle (Zoidl et al., 1995), and can lead to apoptosis in some instances (Fabbretti et al., 1995;Zoidl et al., 1997). Conversely, reduced PMP22 mRNA levels are associated with enhanced DNA synthesis and entry into the S ϩ G2/M phases (Zoidl et al., 1995). In NIH 3T3 fibroblasts, PMP22 overexpression regulates cell spreading, an effect that is dependent on the Rho-GTPase pathway (Brancolini et al., 1999). Recent studies have detected exogenous PMP22 in ADP-ribosylation factor 6 (Arf-6)-positive plasma membrane-endosomal recycling vacuoles before apoptosis or changes in cell shape (Chies et al., 2003). This pathway is known to be involved in modulating the actin cytoskeleton, cell polarity, adhesion, and migration (Donaldson, 2003). Together, these findings support the notion that PMP22 has a significant role in basic cellular processes, extending beyond an involvement in Schwann cell myelination.We previously described PMP22 as a constituent of apical ...

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Peripheral myelin protein 22 is a constituent of intercellular junctions in epithelia

Cited by 91 publications

References 46 publications

Peripheral Myelin Protein 22 Is in Complex with α6β4 Integrin, and Its Absence Alters the Schwann Cell Basal Lamina

Peripheral Myelin Protein 22 Is in Complex with α6β4 Integrin, and Its Absence Alters the Schwann Cell Basal Lamina

Genetic networks responsive to sodium butyrate in colonic epithelial cells

Modulation of Epithelial Morphology, Monolayer Permeability, and Cell Migration by Growth Arrest Specific 3/Peripheral Myelin Protein 22

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