title: Defective axonal transport of neurofilament proteins in neurons overexpressing peripherin.
abstract: Peripherin is a type III neuronal intermediate filament detected in motor neuron inclusions of amyotrophic lateral sclerosis (ALS) patients. We previously reported that overexpression of peripherin provokes late-onset motor neuron dysfunction in transgenic mice. Here, we show that peripherin overexpression slows down axonal transport of neurofilament (NF) proteins, and that the transport defect precedes by several months the appearance of axonal spheroids in adult mice. Defective NF transport by peripherin up-regulation was further confirmed with dorsal root ganglia (DRG) neurons cultured from peripherin transgenic embryos. Immunofluorescence microscopy and western blotting revealed that excess peripherin provokes reduction in levels of hyperphosphorylated NF-H species in DRG neurites. Similarly the transport of a green fluorescent protein (GFP)-tagged NF-M, delivered by means of a lentiviral construct, was impaired in DRG neurites overexpressing peripherin. These results demonstrate that peripherin overexpression can cause defective transport of type IV NF proteins, a phenomenon that may account for the progressive formation of ALS-like spheroids in axons.
authors.affiliation: Research Centre of Centre Hospitalier Universitaire de Québec, Department of Anatomy and Physiology of Laval University, Quebec, Canada.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Millecamps
authors.forename: Janice
authors.initials: J
authors.lastname: Robertson
authors.forename: Roxanne
authors.initials: R
authors.lastname: Lariviere
authors.forename: Jacques
authors.initials: J
authors.lastname: Mallet
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Julien
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001370:Axonal Transport / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007381:Intermediate Filament Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D016900:Neurofilament Proteins / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009924:Organ Culture Techniques; D064531:Peripherins; D018874:Spheroids, Cellular / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; C578994:PRPH protein, human; D064531:Peripherins; C051774:neurofilament protein H; C061195:neurofilament protein M