Linked Life Data

21697510

Source:http://linkedlifedata.com/resource/pubmed/id/21697510

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
2011-7-13
pubmed:abstractText
Homeostatic mechanisms are required to control formation and maintenance of synaptic connections to maintain the general level of neural impulse activity within normal limits. How genes controlling these processes are co-coordinately regulated during homeostatic synaptic plasticity is unknown. MicroRNAs (miRNAs) exert regulatory control over mRNA stability and translation and may contribute to local and activity-dependent posttranscriptional control of synapse-associated mRNAs. However, identifying miRNAs that function through posttranscriptional gene silencing at synapses has remained elusive. Using a bioinformatics screen to identify sequence motifs enriched in the 3'UTR of rapidly destabilized mRNAs, we identified a developmentally and activity-regulated miRNA (miR-485) that controls dendritic spine number and synapse formation in an activity-dependent homeostatic manner. We find that many plasticity-associated genes contain predicted miR-485 binding sites and further identify the presynaptic protein SV2A as a target of miR-485. miR-485 negatively regulated dendritic spine density, postsynaptic density 95 (PSD-95) clustering, and surface expression of GluR2. Furthermore, miR-485 overexpression reduced spontaneous synaptic responses and transmitter release, as measured by miniature excitatory postsynaptic current (EPSC) analysis and FM 1-43 staining. SV2A knockdown mimicked the effects of miR-485, and these effects were reversed by SV2A overexpression. Moreover, 5 d of increased synaptic activity induced homeostatic changes in synaptic specializations that were blocked by a miR-485 inhibitor. Our findings reveal a role for this previously uncharacterized miRNA and the presynaptic protein SV2A in homeostatic plasticity and nervous system development, with possible implications in neurological disorders (e.g., Huntington and Alzheimer's disease), where miR-485 has been found to be dysregulated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11650-5
pubmed:meshHeading
pubmed-meshheading:21697510-3' Untranslated Regions, pubmed-meshheading:21697510-Animals, pubmed-meshheading:21697510-Base Sequence, pubmed-meshheading:21697510-Cells, Cultured, pubmed-meshheading:21697510-Conserved Sequence, pubmed-meshheading:21697510-Dendritic Spines, pubmed-meshheading:21697510-Gene Knockdown Techniques, pubmed-meshheading:21697510-Hippocampus, pubmed-meshheading:21697510-Homeostasis, pubmed-meshheading:21697510-Membrane Glycoproteins, pubmed-meshheading:21697510-MicroRNAs, pubmed-meshheading:21697510-Molecular Sequence Data, pubmed-meshheading:21697510-Nerve Tissue Proteins, pubmed-meshheading:21697510-Neuronal Plasticity, pubmed-meshheading:21697510-Presynaptic Terminals, pubmed-meshheading:21697510-RNA Processing, Post-Transcriptional, pubmed-meshheading:21697510-RNA Stability, pubmed-meshheading:21697510-Rats, pubmed-meshheading:21697510-Sequence Homology, Nucleic Acid
pubmed:year
2011
pubmed:articleTitle
MicroRNA regulation of homeostatic synaptic plasticity.
pubmed:affiliation
Section on Nervous System Development and Plasticity, The Eunice Kennedy Shriver National Institute of Child and Human Development, National Institutes of Health, Bethesda, MD 20892-3714, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural