Alexander D. Blythe
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Alexander D. Blythe has a total of 15 co-authors. Here are the top co-authors by number of shared publications:
- Archi Joardar
Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA
1 shared publication - Bhavani B. Siddegowda
Department of Cellular and Molecular Biology, University of Arizona, Tucson, USA
1 shared publication - Chuol Kueth
Department of Cellular and Molecular Biology, University of Arizona, Tucson, USA
1 shared publication - Daniela C. Zarnescu
Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, USA
1 shared publication - Dianne Barrameda
Department of Cellular and Molecular Biology, University of Arizona, Tucson, USA
1 shared publication - Eric Alsop
Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA
1 shared publication
Latest Publications
- Open Access
- 24 March 2021
- Published by Springer Nature in Acta Neuropathologica Communications
- Vol. 9 (1) , 1-21
TDP-43 proteinopathy alters the ribosome association of multiple mRNAs including the glypican Dally-like protein (Dlp)/GPC6
Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative disease in which 97% of patients exhibit cytoplasmic aggregates containing the RNA binding protein TDP-43. Using tagged ribosome affinity purifications in Drosophila models of TDP-43 proteinopathy, we identified TDP-43 dependent translational alterations in motor neurons impacting the spliceosome, pentose phosphate and oxidative phosphorylation pathways. A subset of the mRNAs with altered ribosome association are also enriched in TDP-43 complexes suggesting that they may be direct targets. Among these, dlp mRNA, which encodes the glypican Dally like protein (Dlp)/GPC6, a wingless (Wg/Wnt) signaling regulator is insolubilized both in flies and patient tissues with TDP-43 pathology. While Dlp/GPC6 forms puncta in the Drosophila neuropil and ALS spinal cords, it is reduced at the neuromuscular synapse in flies suggesting compartment specific effects of TDP-43 proteinopathy. These findings together with genetic interaction data show that Dlp/GPC6 is a novel, physiologically relevant target of TDP-43 proteinopathy.
- 24 March 2021
- Published by Springer Nature in Acta Neuropathologica Communications
- Vol. 9 (1) , 1-21
Open AccessTDP-43 proteinopathy alters the ribosome association of multiple mRNAs including the glypican Dally-like protein (Dlp)/GPC6
Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative disease in which 97% of patients exhibit cytoplasmic aggregates containing the RNA binding protein TDP-43. Using tagged ribosome affinity purifications in Drosophila models of TDP-43 proteinopathy, we identified TDP-43 dependent translational alterations in motor neurons impacting the spliceosome, pentose phosphate and oxidative phosphorylation pathways. A subset of the mRNAs with altered ribosome association are also enriched in TDP-43 complexes suggesting that they may be direct targets. Among these, dlp mRNA, which encodes the glypican Dally like protein (Dlp)/GPC6, a wingless (Wg/Wnt) signaling regulator is insolubilized both in flies and patient tissues with TDP-43 pathology. While Dlp/GPC6 forms puncta in the Drosophila neuropil and ALS spinal cords, it is reduced at the neuromuscular synapse in flies suggesting compartment specific effects of TDP-43 proteinopathy. These findings together with genetic interaction data show that Dlp/GPC6 is a novel, physiologically relevant target of TDP-43 proteinopathy.