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PMP22 accumulation in aggresomes: implications for CMT1A pathology.

Abstract
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.
AuthorsL Notterpek, M C Ryan, A R Tobler, E M Shooter
JournalNeurobiology of disease (Neurobiol Dis) Vol. 6 Issue 5 Pg. 450-60 (Oct 1999) ISSN: 0969-9961 [Print] United States
PMID10527811 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
CopyrightCopyright 1999 Academic Press.
Chemical References
  • Membrane Proteins
  • Myelin and Lymphocyte-Associated Proteolipid Proteins
  • Nerve Tissue Proteins
  • Pllp protein, rat
  • Proteolipids
  • Ubiquitins
  • Vimentin
Topics
  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Charcot-Marie-Tooth Disease (genetics, pathology)
  • Membrane Proteins
  • Myelin and Lymphocyte-Associated Proteolipid Proteins
  • Nerve Tissue Proteins (metabolism)
  • Organelles (metabolism, ultrastructure)
  • Peripheral Nervous System Diseases (pathology, physiopathology)
  • Proteolipids (genetics, metabolism)
  • Rats
  • Schwann Cells (cytology, pathology, physiology)
  • Sciatic Nerve (cytology, physiology)
  • Ubiquitins (analysis)
  • Vimentin (analysis)

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