Nikki Margarita Curthoys1, Hannah Freittag2, Andrea Connor1, Melissa Desouza1, Merryn Brettle3, Anne Poljak4, Amelia Hall3, Edna Hardeman5, Galina Schevzov6, Peter William Gunning6, Thomas Fath7. 1. Neurodegeneration and Repair Unit, School of Medical Sciences, The University of New South Wales, Sydney NSW 2052, Australia; Oncology Research Unit, School of Medical Sciences, The University of New South Wales, Sydney NSW 2052, Australia. 2. Neurodegeneration and Repair Unit, School of Medical Sciences, The University of New South Wales, Sydney NSW 2052, Australia; Neuromuscular and Regenerative Medicine Unit, School of Medical Sciences, The University of New South Wales, Sydney NSW 2052, Australia. 3. Neurodegeneration and Repair Unit, School of Medical Sciences, The University of New South Wales, Sydney NSW 2052, Australia. 4. Bioanalytical Mass Spectrometry Facility, Bioanalytical Centre, The University of New South Wales, Sydney, NSW 2052, Australia. 5. Neuromuscular and Regenerative Medicine Unit, School of Medical Sciences, The University of New South Wales, Sydney NSW 2052, Australia. 6. Oncology Research Unit, School of Medical Sciences, The University of New South Wales, Sydney NSW 2052, Australia. 7. Neurodegeneration and Repair Unit, School of Medical Sciences, The University of New South Wales, Sydney NSW 2052, Australia. Electronic address: t.fath@unsw.edu.au.
Abstract
BACKGROUND: The actin cytoskeleton is critically involved in the regulation of neurite outgrowth. RESULTS: The actin cytoskeleton-associated protein tropomyosin induces neurite outgrowth in B35 neuroblastoma cells and regulates neurite branching in an isoform-dependent manner. CONCLUSIONS: Our data indicate that tropomyosins are key regulators of the actin cytoskeleton during neurite outgrowth. SIGNIFICANCE: Revealing the molecular machinery that regulates the actin cytoskeleton during neurite outgrowth may provide new therapeutic strategies to promote neurite regeneration after nerve injury. SUMMARY: The formation of a branched network of neurites between communicating neurons is required for all higher functions in the nervous system. The dynamics of the actin cytoskeleton is fundamental to morphological changes in cell shape and the establishment of these branched networks. The actin-associated proteins tropomyosins have previously been shown to impact on different aspects of neurite formation. Here we demonstrate that an increased expression of tropomyosins is sufficient to induce the formation of neurites in B35 neuroblastoma cells. Furthermore, our data highlight the functional diversity of different tropomyosin isoforms during neuritogenesis. Tropomyosins differentially impact on the expression levels of the actin filament bundling protein fascin and increase the formation of filopodia along the length of neurites. Our data suggest that tropomyosins are central regulators of actin filament populations which drive distinct aspects of neuronal morphogenesis.
BACKGROUND: The actin cytoskeleton is critically involved in the regulation of neurite outgrowth. RESULTS: The actin cytoskeleton-associated protein tropomyosin induces neurite outgrowth in B35 neuroblastoma cells and regulates neurite branching in an isoform-dependent manner. CONCLUSIONS: Our data indicate that tropomyosins are key regulators of the actin cytoskeleton during neurite outgrowth. SIGNIFICANCE: Revealing the molecular machinery that regulates the actin cytoskeleton during neurite outgrowth may provide new therapeutic strategies to promote neurite regeneration after nerve injury. SUMMARY: The formation of a branched network of neurites between communicating neurons is required for all higher functions in the nervous system. The dynamics of the actin cytoskeleton is fundamental to morphological changes in cell shape and the establishment of these branched networks. The actin-associated proteins tropomyosins have previously been shown to impact on different aspects of neurite formation. Here we demonstrate that an increased expression of tropomyosins is sufficient to induce the formation of neurites in B35 neuroblastoma cells. Furthermore, our data highlight the functional diversity of different tropomyosin isoforms during neuritogenesis. Tropomyosins differentially impact on the expression levels of the actin filament bundling protein fascin and increase the formation of filopodia along the length of neurites. Our data suggest that tropomyosins are central regulators of actin filament populations which drive distinct aspects of neuronal morphogenesis.
Authors: Kevin T Gray; Alexandra K Suchowerska; Tyler Bland; Mert Colpan; Gary Wayman; Thomas Fath; Alla S Kostyukova Journal: Cytoskeleton (Hoboken) Date: 2016-06-08
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