PMP22 Accumulation in Aggresomes: Implications for CMT1A Pathology
Peripheral myelin protein 22 (PMP22) is a 22-kDa glycoprotein mainly expressed by Schwann cells (SCs). Duplication or deletion of the PMP22 gene locus is associated with heritable peripheral neuropathies suggesting that the correct level of PMP22 protein is essential for SC functioning. Previously w...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
1999-10-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996199902747 |
| _version_ | 1818573134826045440 |
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| author | Lucia Notterpek Mary C. Ryan Andreas R. Tobler Eric M. Shooter |
| author_facet | Lucia Notterpek Mary C. Ryan Andreas R. Tobler Eric M. Shooter |
| author_sort | Lucia Notterpek |
| collection | DOAJ |
| description | Peripheral myelin protein 22 (PMP22) is a 22-kDa glycoprotein mainly expressed by Schwann cells (SCs). Duplication or deletion of the PMP22 gene locus is associated with heritable peripheral neuropathies suggesting that the correct level of PMP22 protein is essential for SC functioning. Previously we reported that in SCs the majority (80%) of newly synthesized PMP22 is rapidly degraded, possibly due to inefficient folding. Here we show that inhibition of the proteasome pathway results in a marked accumulation of PMP22 in the perinuclear cytoplasm. Double immunolabeling with an anti-ubiquitin antibody and various organelle markers indicates that the accumulated PMP22 is found in unique intracellular inclusions, called aggresomes. Moreover, overexpression of PMP22 in SCs can induce perinuclear accumulation of the protein. Together, these studies suggest that the proteasome pathway is critical for the regulation of PMP22 protein levels and raise the possibility that aggresomes may be involved in the pathogenesis of PMP22-associated peripheral neuropathies. |
| first_indexed | 2024-12-15T00:07:01Z |
| format | Article |
| id | doaj.art-d95f369203bf4da884dcb13d1d47699d |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-15T00:07:01Z |
| publishDate | 1999-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-d95f369203bf4da884dcb13d1d47699d2022-12-21T22:42:42ZengElsevierNeurobiology of Disease1095-953X1999-10-0165450460PMP22 Accumulation in Aggresomes: Implications for CMT1A PathologyLucia Notterpek0Mary C. Ryan1Andreas R. Tobler2Eric M. Shooter3Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305Peripheral myelin protein 22 (PMP22) is a 22-kDa glycoprotein mainly expressed by Schwann cells (SCs). Duplication or deletion of the PMP22 gene locus is associated with heritable peripheral neuropathies suggesting that the correct level of PMP22 protein is essential for SC functioning. Previously we reported that in SCs the majority (80%) of newly synthesized PMP22 is rapidly degraded, possibly due to inefficient folding. Here we show that inhibition of the proteasome pathway results in a marked accumulation of PMP22 in the perinuclear cytoplasm. Double immunolabeling with an anti-ubiquitin antibody and various organelle markers indicates that the accumulated PMP22 is found in unique intracellular inclusions, called aggresomes. Moreover, overexpression of PMP22 in SCs can induce perinuclear accumulation of the protein. Together, these studies suggest that the proteasome pathway is critical for the regulation of PMP22 protein levels and raise the possibility that aggresomes may be involved in the pathogenesis of PMP22-associated peripheral neuropathies.http://www.sciencedirect.com/science/article/pii/S0969996199902747Schwann cellsneuropathyubiquitinproteasomelactacystin. |
| spellingShingle | Lucia Notterpek Mary C. Ryan Andreas R. Tobler Eric M. Shooter PMP22 Accumulation in Aggresomes: Implications for CMT1A Pathology Neurobiology of Disease Schwann cells neuropathy ubiquitin proteasome lactacystin. |
| title | PMP22 Accumulation in Aggresomes: Implications for CMT1A Pathology |
| title_full | PMP22 Accumulation in Aggresomes: Implications for CMT1A Pathology |
| title_fullStr | PMP22 Accumulation in Aggresomes: Implications for CMT1A Pathology |
| title_full_unstemmed | PMP22 Accumulation in Aggresomes: Implications for CMT1A Pathology |
| title_short | PMP22 Accumulation in Aggresomes: Implications for CMT1A Pathology |
| title_sort | pmp22 accumulation in aggresomes implications for cmt1a pathology |
| topic | Schwann cells neuropathy ubiquitin proteasome lactacystin. |
| url | http://www.sciencedirect.com/science/article/pii/S0969996199902747 |
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