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Mouse Cytoplasmic Dynein Intermediate Chains: Identification of New Isoforms, Alternative Splicing and Tissue Distribution of Transcripts

Kuta, A; Deng, WH; El-Kadi, AM; Banks, GT; Hafezparast, M; Pfister, KK; Fisher, EMC; (2010) Mouse Cytoplasmic Dynein Intermediate Chains: Identification of New Isoforms, Alternative Splicing and Tissue Distribution of Transcripts. PLOS ONE , 5 (7) , Article e11682. 10.1371/journal.pone.0011682. Green open access

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Abstract

Background: Intracellular transport of cargoes including organelles, vesicles, signalling molecules, protein complexes, and RNAs, is essential for normal function of eukaryotic cells. The cytoplasmic dynein complex is an important motor that moves cargos along microtubule tracks within the cell. In mammals this multiprotein complex includes dynein intermediate chains 1 and 2 which are encoded by two genes, Dync1i1 and Dync1i2. These proteins are involved in dynein cargo binding and dynein complexes with different intermediate chains bind to specific cargoes, although the mechanisms to achieve this are not known. The DYNC1I1 and DYNC1I2 proteins are translated from different splice isoforms, and specific forms of each protein are essential for the function of different dynein complexes in neurons.Methodology/Principal Findings: Here we have undertaken a systematic survey of the dynein intermediate chain splice isoforms in mouse, basing our study on mRNA expression patterns in a range of tissues, and on bioinformatics analysis of mouse, rat and human genomic and cDNA sequences. We found a complex pattern of alternative splicing of both dynein intermediate chain genes, with maximum complexity in the embryonic and adult nervous system. We have found novel transcripts, including some with orthologues in human and rat, and a new promoter and alternative non-coding exon 1 for Dync1i2.Conclusions/Significance: These data, including the cloned isoforms will be essential for understanding the role of intermediate chains in the cytoplasmic dynein complex, particularly their role in cargo binding within individual tissues including different brain regions.

Type: Article
Title: Mouse Cytoplasmic Dynein Intermediate Chains: Identification of New Isoforms, Alternative Splicing and Tissue Distribution of Transcripts
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0011682
Publisher version: http://dx.doi.org/10.1371/journal.pone.0011682
Language: English
Additional information: © 2010 Kuta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. These authors are supported by the Wellcome Trust, the ENDOCYTE Research and Training Network funded by the European Union and the UK Medical Research Council and the National Institute of General Medical Science (National Institutes of Health). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: DIFFERENTIAL EXPRESSION, LIGHT-CHAINS, HUMAN GENES, ARM DYNEIN, BINDS, MOTOR, TRANSPORT, SUBUNIT, DYNACTIN, PHOSPHORYLATION
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/126767
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