Neurons Promote the Translocation of Peripheral Myelin Protein 22 into Myelin

Pareek, Sangeeta; Notterpek, Lucia; Gj, Snipes; Naef, Roland; Sossin, Wayne S.; Laliberté, Jean‐François; Iacampo, Sandra; Suter, Ueli; Shooter, E. M.; Ra, Murphy

doi:10.1523/jneurosci.17-20-07754.1997

Cited by 139 publications

(212 citation statements)

References 49 publications

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“…In DMSO carrier-treated cells, PMP22 is detected at low levels in the ER and Golgi apparatus, and at the plasma membrane (Fig. 5A, DMSO inset, also see Pareek et al, 1997). When simultaneous to proteasome inhibition, autophagy is enhanced (starvation, Stv), fewer cells form aggregates (Fig.…”

Section: The Formation Of Aggresomes Is Hindered By Autophagymentioning

confidence: 88%

“…In non-myelinating and myelinating SCs, the majority (~80%) of the newly-synthesized PMP22 is rapidly degraded by the UPS, presumably due to misfolding (Pareek et al, 1997). Mutations in PMP22, or duplication of the PMP22 gene, are associated with hereditary demyelinating neuropathies among which, Charcot Marie Tooth type 1A (CMT1A) is the most common form (Young and Suter, 2001).…”

Section: Introductionmentioning

confidence: 99%

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The formation of peripheral myelin protein 22 aggregates is hindered by the enhancement of autophagy and expression of cytoplasmic chaperones

Fortun

Verrier

et al. 2007

Neurobiology of Disease

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The accumulation of misfolded proteins is associated with various neurodegenerative conditions. Peripheral myelin protein 22 (PMP22) is a hereditary neuropathy-linked, short-lived molecule that forms aggresomes when the proteasome is inhibited or the protein is mutated. We previously showed that the removal of pre-existing PMP22 aggregates is assisted by autophagy. Here we examined whether the accumulation of such aggregates could be suppressed by experimental induction of autophagy and/or chaperones. Enhancement of autophagy during proteasome inhibition hinders protein aggregate formation and correlates with a reduction in accumulated proteasome substrates. Conversely, simultaneous inhibition of autophagy and the proteasome augments the formation of aggregates. An increase of heat shock protein levels by geldanamycin treatment or heat shock preconditioning similarly hampers aggresome formation. The beneficial effects of autophagy and chaperones in preventing the accumulation of misfolded PMP22 are additive and provide a potential avenue for therapeutic approaches in hereditary neuropathies linked to PMP22 mutations.

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Section: The Formation Of Aggresomes Is Hindered By Autophagymentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

The formation of peripheral myelin protein 22 aggregates is hindered by the enhancement of autophagy and expression of cytoplasmic chaperones

Fortun

Verrier

et al. 2007

Neurobiology of Disease

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101

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“…1 and step 1a), may be refolded by molecular chaperones at the endoplasmic reticulum (ER) 13 ( Fig. 1 and step 2).…”

Section: The Proteasome and Aggresome-autophagy Pathways Protect Schwmentioning

confidence: 99%

“…1 and step 5) that inhibit proteasome function ( Fig. 1 and step 6 ) and may impair Schwann cell functions including myelination 13,14 ( Fig. 1 and step 7).…”

confidence: 99%

Protein misfolding and clearance in demyelinating peripheral neuropathies

Lee

Chin

2012

Communicative & Integrative Biology

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“…For Western blotting, monolayers of confluent MDCK cells were lysed (Notterpek et al, 2001), and where indicated, treated with N-glycosidase (PNGase F) (Pareek et al, 1997). Samples were separated by SDS-PAGE and transferred to nitrocellulose membrane (Bio-Rad, Hercules, CA) before immunoblotting.…”

Section: Cell Surface Biotinylation and Western Blottingmentioning

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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Neurons Promote the Translocation of Peripheral Myelin Protein 22 into Myelin

Cited by 139 publications

References 49 publications

The formation of peripheral myelin protein 22 aggregates is hindered by the enhancement of autophagy and expression of cytoplasmic chaperones

The formation of peripheral myelin protein 22 aggregates is hindered by the enhancement of autophagy and expression of cytoplasmic chaperones

Protein misfolding and clearance in demyelinating peripheral neuropathies

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

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