Poster abstracts

Poster number 88 submitted by Patrick Heilman

Characterization of a Motor Neuropathy-Associated Mutation in HSPB3

Patrick L. Heilman (Molecular and Cellular Biochemistry, OSU), Stephen J. Kolb (Molecular and Cellular Biochemistry, Neurology, OSU)

Abstract:
Hereditary neuropathies, or Charcot-Marie-Tooth disease, are some of the most common inherited human neurological disorders, affecting approximately 1 in 2,500 people in the United States. There at least 50 genes identified that, when mutated, result in neuropathy [1, 2]. Though these genes are diverse, many appear to involve the disruption of native protein-protein interactions. Intriguingly, three of the ten small heat shock proteins (sHSPs) expressed in humans have been associated with hereditary motor neuropathies. Designated HSPB1, HSPB3 and HSPB8, these small proteins readily interact with other sHSPs to form homo- and hetero-oligomeric complexes [3]. Of these 3 proteins, HSPB3 remains the least understood. The development of an axonal motor neuropathy characterized by adult-onset, slowly progressive distal arm and leg weakness is associated with a missense mutation, R7S, in the N-terminal region of HSPB3 [4]. In this study, we investigate the interaction between mutant HSPB3 and other sHSPs using co-immunoprecipitation and immunofluorescence techniques. We find alterations in the protein interactome of wild type HSPB3 compared to mutant HSPB3. We propose that this disruption in sHSP interactions plays a mechanistic role in the associated motor neuropathies.

References:
1. Gess, B., A. Schirmacher, and P. Young, [Genetics of neuropathies]. Nervenarzt, 2013. 84(2): p. 157-65.
2. Rossor, A.M., et al., The distal hereditary motor neuropathies. J Neurol Neurosurg Psychiatry, 2012. 83(1): p. 6-14.
3. Delbecq, S.P. and R.E. Klevit, One size does not fit all: The oligomeric states of alpha B crystallin. Febs Letters, 2013. 587(8): p. 1073-1080.
4. Kolb, S.J., et al., Mutant small heat shock protein B3 causes motor neuropathy: utility of a candidate gene approach. Neurology, 2010. 74(6): p. 502-6.

Keywords: Small Heat Shock Proteins, HSPB3, Motor Neuropathies