rdf:type |
|
lifeskim:mentions |
umls-concept:C0039065,
umls-concept:C0302523,
umls-concept:C0439851,
umls-concept:C0599896,
umls-concept:C0700325,
umls-concept:C1514873,
umls-concept:C1546857,
umls-concept:C1552596,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C1947931
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pubmed:issue |
7
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pubmed:dateCreated |
2005-4-12
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pubmed:abstractText |
Axonal transport is required for the elaboration and maintenance of synaptic morphology and function. Liprin-alphas are scaffolding proteins important for synapse structure and electrophysiology. A reported interaction with Kinesin-3 (Kif1a) suggested Liprin-alpha may also be involved in axonal transport. Here, at the light and ultrastructural levels, we discover aberrant accumulations of synaptic vesicle markers (Synaptotagmin and Synaptobrevin-GFP) and clear-core vesicles along Drosophila Liprin-alpha mutant axons. Analysis of presynaptic markers reveals reduced levels at Liprin-alpha synapses. Direct visualization of Synaptobrevin-GFP transport in living animals demonstrates a decrease in anterograde processivity in Liprin-alpha mutants but also an increase in retrograde transport initiation. Pull-down assays reveal that Liprin-alpha interacts with Drosophila Kinesin-1 (Khc) but not dynein. Together, these findings suggest that Liprin-alpha promotes the delivery of synaptic material by a direct increase in kinesin processivity and an indirect suppression of dynein activation. This work is the first to use live observation in Drosophila mutants to demonstrate the role of a scaffolding protein in the regulation of bidirectional transport. It suggests the synaptic strength and morphology defects linked to Liprin-alpha may in part be due to a failure in the delivery of synaptic-vesicle precursors.
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pubmed:grant |
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Kinesin,
http://linkedlifedata.com/resource/pubmed/chemical/Liprin-alpha protein, Drosophila,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/R-SNARE Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Synaptotagmins
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
|
pubmed:issn |
0960-9822
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
12
|
pubmed:volume |
15
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
684-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15823543-Animals,
pubmed-meshheading:15823543-Axonal Transport,
pubmed-meshheading:15823543-Calcium-Binding Proteins,
pubmed-meshheading:15823543-Drosophila Proteins,
pubmed-meshheading:15823543-Drosophila melanogaster,
pubmed-meshheading:15823543-Glutathione Transferase,
pubmed-meshheading:15823543-Green Fluorescent Proteins,
pubmed-meshheading:15823543-Kinesin,
pubmed-meshheading:15823543-Membrane Glycoproteins,
pubmed-meshheading:15823543-Membrane Proteins,
pubmed-meshheading:15823543-Microscopy, Electron,
pubmed-meshheading:15823543-Nerve Tissue Proteins,
pubmed-meshheading:15823543-Phosphoproteins,
pubmed-meshheading:15823543-R-SNARE Proteins,
pubmed-meshheading:15823543-Synapses,
pubmed-meshheading:15823543-Synaptic Vesicles,
pubmed-meshheading:15823543-Synaptotagmins
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pubmed:year |
2005
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pubmed:articleTitle |
Direct observation demonstrates that Liprin-alpha is required for trafficking of synaptic vesicles.
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pubmed:affiliation |
Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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