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

@article{citeulike:4643157, 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.}, author = {Siegel, G. and Obernosterer, G. and Fiore, R. and Oehmen, M. and Bicker, S. and Christensen, M. and Khudayberdiev, S. and Leuschner, P. F. and Busch, C. J. and Kane, C. and H\"{u}bel, K. and Dekker, F. and Hedberg, C. and Rengarajan, B. and Drepper, C. and Waldmann, H. and Kauppinen, S. and Greenberg, M. E. and Draguhn, A. and Rehmsmeier, M. and Martinez, J. and Schratt, G. M.}, citeulike-article-id = {4643157}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/ncb1876}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/ncb1876}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19465924}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19465924}, day = {24}, doi = {10.1038/ncb1876}, issn = {1476-4679}, journal = {Nature cell biology}, keywords = {apt1, mir-138}, month = {June}, number = {6}, pages = {705--716}, posted-at = {2009-06-16 19:48:00}, priority = {2}, title = {A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis.}, url = {http://dx.doi.org/10.1038/ncb1876}, volume = {11}, year = {2009} }

TY - JOUR ID - citeulike:4643157 L3 - citeulike-article-id:4643157 N2 - 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. IS - 6 JF - Nature cell biology SN - 1476-4679 EP - 716 TI - A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis. VL - 11 SP - 705 KW - apt1 KW - mir-138 AU - Siegel, G AU - Obernosterer, G AU - Fiore, R AU - Oehmen, M AU - Bicker, S AU - Christensen, M AU - Khudayberdiev, S AU - Leuschner, PF AU - Busch, CJ AU - Kane, C AU - Hübel, K AU - Dekker, F AU - Hedberg, C AU - Rengarajan, B AU - Drepper, C AU - Waldmann, H AU - Kauppinen, S AU - Greenberg, ME AU - Draguhn, A AU - Rehmsmeier, M AU - Martinez, J AU - Schratt, GM PY - 2009/06/24/ UR - http://dx.doi.org/10.1038/ncb1876 ER -