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Nat Cell Biol. 2009 Jun;11(6):705-16. doi: 10.1038/ncb1876. Epub 2009 May 24.

A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis.

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  • 1Interdisziplinäres Zentrum für Neurowissenschaften, SFB488 Junior Group, Universität Heidelberg, and Institut für Neuroanatomie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.

Abstract

The microRNA pathway has been implicated in the regulation of synaptic protein synthesis and ultimately in dendritic spine morphogenesis, a phenomenon associated with long-lasting forms of memory. However, the particular microRNAs (miRNAs) involved are largely unknown. Here we identify specific miRNAs that function at synapses to control dendritic spine structure by performing a functional screen. One of the identified miRNAs, miR-138, is highly enriched in the brain, localized within dendrites and negatively regulates the size of dendritic spines in rat hippocampal neurons. miR-138 controls the expression of acyl protein thioesterase 1 (APT1), an enzyme regulating the palmitoylation status of proteins that are known to function at the synapse, including the alpha(13) subunits of G proteins (Galpha(13)). RNA-interference-mediated knockdown of APT1 and the expression of membrane-localized Galpha(13) both suppress spine enlargement caused by inhibition of miR-138, suggesting that APT1-regulated depalmitoylation of Galpha(13) might be an important downstream event of miR-138 function. Our results uncover a previously unknown miRNA-dependent mechanism in neurons and demonstrate a previously unrecognized complexity of miRNA-dependent control of dendritic spine morphogenesis.

PMID:
19465924
[PubMed - indexed for MEDLINE]
PMCID:
PMC3595613
Free PMC Article
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