1. A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis
- Author
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Siegel, Gabriele, Obernosterer, Gregor, Fiore, Roberto, Oehmen, Martin, Bicker, Silvia, Christensen, Mette, Khudayberdiev, Sharof, Leuschner, Philipp F, Busch, Clara J L, Kane, Christina, Hübel, Katja, Dekker, Frank, Hedberg, Christian, Rengarajan, Balamurugan, Drepper, Carsten, Waldmann, Herbert, Kauppinen, Sakari, Greenberg, Michael E, Draguhn, Andreas, Rehmsmeier, Marc, Martinez, Javier, Schratt, Gerhard M, Siegel, Gabriele, Obernosterer, Gregor, Fiore, Roberto, Oehmen, Martin, Bicker, Silvia, Christensen, Mette, Khudayberdiev, Sharof, Leuschner, Philipp F, Busch, Clara J L, Kane, Christina, Hübel, Katja, Dekker, Frank, Hedberg, Christian, Rengarajan, Balamurugan, Drepper, Carsten, Waldmann, Herbert, Kauppinen, Sakari, Greenberg, Michael E, Draguhn, Andreas, Rehmsmeier, Marc, Martinez, Javier, and Schratt, Gerhard M
- Abstract
Udgivelsesdato: 2009-Jun, 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.
- Published
- 2009