Source:http://linkedlifedata.com/resource/pubmed/id/20147321
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
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| pubmed:dateCreated |
2010-4-8
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| pubmed:abstractText |
The small signalling adaptor protein Dok-7 has recently been reported as an essential protein of the neuromuscular junction (NMJ). Mutations resulting in partial loss of Dok-7 activity cause a distinct limb-girdle subtype of the inherited NMJ disorder congenital myasthenic syndromes (CMSs), whereas complete loss of Dok-7 results in a lethal phenotype in both mice and humans. Here we describe the zebrafish orthologue of Dok-7 and study its in vivo function. Dok-7 deficiency leads to motility defects in zebrafish embryos and larvae. The relative importance of Dok-7 at different stages of NMJ development varies; it is crucial for the earliest step, the formation of acetylcholine receptor (AChR) clusters in the middle of the muscle fibre prior to motor neuron contact. At later stages, presence of Dok-7 is not absolutely essential, as focal and non-focal synapses do form when Dok-7 expression is downregulated. These contacts however are smaller than in the wild-type zebrafish, reminiscent of the neuromuscular endplate pathology seen in patients with DOK7 mutations. Intriguingly, we also observed changes in slow muscle fibre arrangement; previously, Dok-7 has not been linked to functions other than postsynaptic AChR clustering. Our results suggest an additional role of Dok-7 in muscle. This role seems to be independent of the muscle-specific tyrosine kinase MuSK, the known binding partner of Dok-7 at the NMJ. Our findings in the zebrafish model contribute to a better understanding of the signalling pathways at the NMJ and the pathomechanisms of DOK7 CMSs.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cholinergic,
http://linkedlifedata.com/resource/pubmed/chemical/Zebrafish Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
1460-2083
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
1
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| pubmed:volume |
19
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1726-40
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| pubmed:meshHeading |
pubmed-meshheading:20147321-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:20147321-Amino Acid Sequence,
pubmed-meshheading:20147321-Animals,
pubmed-meshheading:20147321-Base Sequence,
pubmed-meshheading:20147321-DNA Primers,
pubmed-meshheading:20147321-Fluorescent Antibody Technique,
pubmed-meshheading:20147321-Gene Components,
pubmed-meshheading:20147321-Gene Expression Regulation,
pubmed-meshheading:20147321-In Situ Hybridization,
pubmed-meshheading:20147321-Molecular Sequence Data,
pubmed-meshheading:20147321-Muscle, Skeletal,
pubmed-meshheading:20147321-Muscle Proteins,
pubmed-meshheading:20147321-Myasthenic Syndromes, Congenital,
pubmed-meshheading:20147321-Neuromuscular Junction,
pubmed-meshheading:20147321-Receptors, Cholinergic,
pubmed-meshheading:20147321-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20147321-Sequence Alignment,
pubmed-meshheading:20147321-Sequence Analysis, DNA,
pubmed-meshheading:20147321-Signal Transduction,
pubmed-meshheading:20147321-Zebrafish,
pubmed-meshheading:20147321-Zebrafish Proteins
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| pubmed:year |
2010
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| pubmed:articleTitle |
Dok-7 promotes slow muscle integrity as well as neuromuscular junction formation in a zebrafish model of congenital myasthenic syndromes.
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| pubmed:affiliation |
Institute of Human Genetics, International Centre for Life, Newcastle University, Central Parkway, Newcastle Upon Tyne NE1 3BZ, UK. juliane.mueller@ncl.ac.uk
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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