Mutant HSPB8 causes motor neuron-specific neurite degeneration
| Autor: | Vincent Timmerman, Jean-Pierre Timmermans, Leonardo Almeida-Souza, Peter De Jonghe, J. Krishnan, Sofie Goethals, Ludo Van Den Bosch, Wim Robberecht, Sophie Janssens, Bob Asselbergh, Vicky De Winter, Ines Dierick, Joy Irobi |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Neurite
Mutant Blotting Western Green Fluorescent Proteins Muscle Proteins Apoptosis medicine.disease_cause Transfection Amyloid beta-Protein Precursor Mice Cell Line Tumor Genetics Amyloid precursor protein medicine In Situ Nick-End Labeling Neurites Animals Humans HSP20 Heat-Shock Proteins Rats Wistar Molecular Biology Genetics (clinical) Cells Cultured Heat-Shock Proteins Motor Neurons Mutation Microscopy Confocal biology General Medicine Articles Motor neuron Phenotype Immunohistochemistry Cell biology Rats Tissue Degeneration Mice Inbred C57BL medicine.anatomical_structure Amino Acid Substitution nervous system biology.protein Neuroglia Human medicine DNA Damage Molecular Chaperones |
| Zdroj: | Human molecular genetics Human Molecular Genetics |
| ISSN: | 0964-6906 |
| Popis: | Missense mutations (K141N and K141E) in the {alpha}-crystallin domain of the small heat shock protein HSPB8 (HSP22) cause distal hereditary motor neuropathy (distal HMN) or Charcot-Marie-Tooth neuropathy type 2L (CMT2L). The mechanism through which mutant HSPB8 leads to a specific motor neuron disease phenotype is currently unknown. To address this question, we compared the effect of mutant HSPB8 in primary neuronal and glial cell cultures. In motor neurons, expression of both HSPB8 K141N and K141E mutations clearly resulted in neurite degeneration, as manifested by a reduction in number of neurites per cell, as well as in a reduction in average length of the neurites. Furthermore, expression of the K141E (and to a lesser extent, K141N) mutation also induced spheroids in the neurites. We did not detect any signs of apoptosis in motor neurons, showing that mutant HSPB8 resulted in neurite degeneration without inducing neuronal death. While overt in motor neurons, these phenotypes were only very mildly present in sensory neurons and completely absent in cortical neurons. Also glial cells did not show an altered phenotype upon expression of mutant HSPB8. These findings show that despite the ubiquitous presence of HSPB8, only motor neurons appear to be affected by the K141N and K141E mutations which explain the predominant motor neuron phenotype in distal HMN and CMT2L. |
| Databáze: | OpenAIRE |
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