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Defective axonal transport of neurofilament proteins in neurons overexpressing peripherin
Author(s) -
Millecamps Stéphanie,
Robertson Janice,
Lariviere Roxanne,
Mallet Jacques,
Julien JeanPierre
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03932.x
Subject(s) - peripherin , neurofilament , microbiology and biotechnology , axoplasmic transport , intermediate filament , biology , neurite , amyotrophic lateral sclerosis , motor neuron , genetically modified mouse , transgene , neuroscience , pathology , cytoskeleton , medicine , spinal cord , immunology , genetics , gene , immunohistochemistry , disease , cell , in vitro
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.