Neuronal Function and Dysfunction of Drosophila dTDP
- Publication Date
- June 01, 2011
- Journal
- PLOS ONE
- Authors
- Meng Jau Lin, Ching Wei Cheng & C. K. James Shen
- Volume
- 6
- Issue
- 6
- Pages
- e20371
- DOI
- https://dx.plos.org/10.1371/journal.pone.0020371
- Publisher URL
- http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0020371
- PubMed
- http://www.ncbi.nlm.nih.gov/pubmed/21673800
- PubMed Central
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105987
- Europe PMC
- http://europepmc.org/abstract/MED/21673800
- Web of Science
- 000291309900015
- Scopus
- 79957801387
- Mendeley
- http://www.mendeley.com/research/neuronal-function-dysfunction-drosophila-dtdp
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Mendeley | Further Information
{"title"=>"Neuronal function and dysfunction of drosophila dTDP", "type"=>"journal", "authors"=>[{"first_name"=>"Meng Jau", "last_name"=>"Lin", "scopus_author_id"=>"37042007600"}, {"first_name"=>"Ching Wei", "last_name"=>"Cheng", "scopus_author_id"=>"56309736900"}, {"first_name"=>"C. K James", "last_name"=>"Shen", "scopus_author_id"=>"7402860269"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-79957801387", "pui"=>"361862764", "doi"=>"10.1371/journal.pone.0020371", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"79957801387", "pmid"=>"21673800"}, "id"=>"e0e6c697-de52-3db6-be83-261f0da6b598", "abstract"=>"BACKGROUND: TDP-43 is an RNA- and DNA-binding protein well conserved in animals including the mammals, Drosophila, and C. elegans. In mammals, the multi-function TDP-43 encoded by the TARDBP gene is a signature protein of the ubiquitin-positive inclusions (UBIs) in the diseased neuronal/glial cells of a range of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-U).\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: We have studied the function and dysfunction of the Drosophila ortholog of the mammalian TARDBP gene, dTDP, by genetic, behavioral, molecular, and cytological analyses. It was found that depletion of dTDP expression caused locomotion defect accompanied with an increase of the number of boutons at the neuromuscular junctions (NMJ). These phenotypes could be rescued by overexpression of Drosophila dTDP in the motor neurons. In contrast, overexpression of dTDP in the motor neurons also resulted in reduced larval and adult locomotor activities, but this was accompanied by a decrease of the number of boutons and axon branches at NMJ. Significantly, constitutive overexpression of dTDP in the mushroom bodies caused smaller axonal lobes as well as severe learning deficiency. On the other hand, constitutive mushroom body-specific knockdown of dTDP expression did not affect the structure of the mushroom bodies, but it impaired the learning ability of the flies, albeit moderately. Overexpression of dTDP also led to the formation of cytosolic dTDP (+) aggregates.\\n\\nCONCLUSION/SIGNIFICANCE: These data together demonstrate the neuronal functions of dTDP, and by implication the mammalian TDP-43, in learning and locomotion. The effects of mis-expression of dTDP on Drosophila NMJ suggest that eukaryotic TDP-43 guards against over development of the synapses. The conservation of the regulatory pathways of functions and dysfunctions of Drosophila dTDP and mammalian TDP-43 also shows the feasibility of using the flies as a model system for studying the normal TDP-43 function and TDP-43 proteinopathies in the vertebrates including human.", "link"=>"http://www.mendeley.com/research/neuronal-function-dysfunction-drosophila-dtdp", "reader_count"=>52, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>5, "Researcher"=>16, "Student > Ph. D. Student"=>15, "Student > Master"=>3, "Other"=>3, "Student > Bachelor"=>4, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>5, "Researcher"=>16, "Student > Ph. D. Student"=>15, "Student > Master"=>3, "Other"=>3, "Student > Bachelor"=>4, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Nursing and Health Professions"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>30, "Medicine and Dentistry"=>11, "Neuroscience"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>11}, "Neuroscience"=>{"Neuroscience"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>30}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Japan"=>1, "China"=>1, "United Kingdom"=>3, "Italy"=>1}, "group_count"=>1}CrossRef
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Relative Metric
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