Characterisation of syncoilin

Thesis

Syncoilin is a 64kDa intermediate filament protein (IF) first studied because it binds to the dystrophin associated protein complex (DAPC) through α-dystrobrevin. Syncoilin is highly expressed in skeletal and cardiac muscle, but the function of syncoilin in muscle remains largely unknown. A recently generated syncoilin null (sync-/-) mouse has almost no muscle phenotype. This thesis makes significant progress in characterising the function of syncoilin in muscle and nerve and discovering a phenotype in the sync-/- mouse. The first half of this thesis attempts to further elucidate the function of syncoilin in muscle. Two new syncoilin isoforms were discovered in muscle, and syncoilin was shown to be upregulated in muscle during atrophy and regeneration. Sync+/+ and sync-/- primary muscle cell lines were generated in an attempt to elucidate a signalling role for syncoilin in muscle, but no difference was discovered between the two cell lines in cell growth, drug resistance or protein synthesis. Recent discoveries from this laboratory reveal that syncoilin is also expressed in neurons. The second half of this thesis is an attempt to characterise the function of syncoilin in neurons. Two potential syncoilin neuronal binding partners were examined. Syncoilin and α-tubulin bind via co-immunoprecipitation, but there is no co-localisation between the two proteins in sciatic nerve. Peripherin was shown to co-localise with syncoilin in sciatic nerve, and co-transfections suggest that syncoilin acts to regulate peripherin filament formation. Finally, a neuronal analysis of the sync-/- mouse shows decreased motor function in a range of behavioural tests. This observation is confirmed with the discovery that motor neurons in the sync-/- mouse have decreased axon calibre when compared to the sync+/+ mouse. The possibility that syncoilin plays a vital role in neuronal function is a significant discovery and opens an exciting new avenue of research.

Authors: Clarke, W

• Publication date: 2009
• Type of award: MSc
• Level of award: Masters
• Awarding institution: Oxford University, UK
• Language: English
• Keywords: ventral root; amyotrophic lateral sclerosis; syncoilin; neurons; axon caliber; peripherin; intermediate filaments
• Subjects: Physiology and anatomy; Biology; Life Sciences