1. A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis
- Author
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Sakari Kauppinen, Clara J L Busch, Andreas Draguhn, Katja Hübel, Frank J. Dekker, Christian Hedberg, Herbert Waldmann, Marc Rehmsmeier, Gerhard Schratt, Balamurugan Rengarajan, Javier Martinez, Gregor Obernosterer, Silvia Bicker, Gabriele Siegel, Philipp F Leuschner, Christina G. Kane, Sharof Khudayberdiev, Carsten Drepper, Martin Oehmen, Michael E. Greenberg, Mette Christensen, Roberto Fiore, and University of Zurich
- Subjects
Dendritic spine ,G protein ,Dendritic Spines ,Lipoylation ,Molecular Sequence Data ,Morphogenesis ,Dendritic spine morphogenesis ,610 Medicine & health ,Biology ,GTP-Binding Protein alpha Subunits, G12-G13 ,Hippocampus ,Article ,Cell Line ,1307 Cell Biology ,Synapse ,Mice ,Palmitoylation ,microRNA ,Animals ,Humans ,Oligonucleotide Array Sequence Analysis ,Neurons ,Gene knockdown ,Base Sequence ,Gene Expression Profiling ,11359 Institute for Regenerative Medicine (IREM) ,Cell Biology ,Rats ,Cell biology ,Mice, Inbred C57BL ,MicroRNAs ,Receptors, Glutamate ,Synapses ,Thiolester Hydrolases - 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 (G alpha(13)). RNA-interference-mediated knockdown of APT1 and the expression of membrane-localized G alpha(13) both suppress spine enlargement caused by inhibition of miR-138, suggesting that APT1-regulated depalmitoylation of G alpha(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.
- Published
- 2009