Title: Mutant HSPB8 causes motor neuron specific neurite degeneration
Authors: Irobi, Joy ×
Almeida-Souza, Leonardo
Asselbergh, Bob
De Winter, Vicky
Goethals, Sofie
Dierick, Ines
Krishnan, Jyothsna
Timmermans, J
Robberecht, Wim
De Jonghe, Peter
Van Den Bosch, Ludo
Janssens, Sophie
Timmerman, Vincent #
Issue Date: Aug-2010
Publisher: IRL Press
Series Title: Human Molecular Genetics vol:19 issue:16 pages:3254-3265
Abstract: 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 explains the predominant motor neuron phenotype in distal HMN and CMT2L.
ISSN: 0964-6906
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Neurology
Laboratory for Neurobiology (Vesalius Research Center)
× corresponding author
# (joint) last author

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