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

Gabriele Siegel; Gregor Obernosterer; Roberto Fiore; Martin Oehmen; Silvia Bicker; Mette Christensen; Sharof Khudayberdiev; Philipp F Leuschner; Clara J L Busch; Christina Kane; Katja Hübel; Frank Dekker; Christian Hedberg; Balamurugan Rengarajan; Carsten Drepper; Herbert Waldmann; Sakari Kauppinen; Michael E Greenberg; Andreas Draguhn; Marc Rehmsmeier; Javier Martinez; Gerhard M Schratt

doi:10.1038/ncb1876

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

Gabriele Siegel, Gregor Obernosterer, Roberto Fiore, Martin Oehmen, Silvia Bicker, Mette Christensen, Sharof Khudayberdiev, Philipp F Leuschner, Clara J L Busch, Christina Kane, Katja Hübel, Frank Dekker, Christian Hedberg, Balamurugan Rengarajan, Carsten Drepper, Herbert Waldmann, Sakari Kauppinen, Michael E Greenberg, Andreas Draguhn, Marc RehmsmeierJavier Martinez, Gerhard M Schratt

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

416 Citationer (Scopus)

Abstract

Udgivelsesdato: 2009-Jun

Originalsprog	Engelsk
Tidsskrift	Nature Cell Biology
Vol/bind	11
Udgave nummer	6
Sider (fra-til)	705-16
Antal sider	11
ISSN	1465-7392
DOI	https://doi.org/10.1038/ncb1876
Status	Udgivet - 2009

Bibliografisk note

Keywords: Animals; Base Sequence; Cell Line; Dendritic Spines; GTP-Binding Protein alpha Subunits, G12-G13; Gene Expression Profiling; Hippocampus; Humans; Lipoylation; Mice; Mice, Inbred C57BL; MicroRNAs; Molecular Sequence Data; Morphogenesis; Neurons; Oligonucleotide Array Sequence Analysis; Rats; Receptors, Glutamate; Synapses; Thiolester Hydrolases

Adgang til dokumentet

10.1038/ncb1876

Citationsformater

Siegel, G., Obernosterer, G., Fiore, R., Oehmen, M., Bicker, S., Christensen, M., Khudayberdiev, S., Leuschner, P. F., Busch, C. J. L., Kane, C., Hübel, K., Dekker, F., Hedberg, C., Rengarajan, B., Drepper, C., Waldmann, H., Kauppinen, S., Greenberg, M. E., Draguhn, A., ... Schratt, G. M. (2009). A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis. Nature Cell Biology, 11(6), 705-16. https://doi.org/10.1038/ncb1876

Siegel, G, Obernosterer, G, Fiore, R, Oehmen, M, Bicker, S, Christensen, M, Khudayberdiev, S, Leuschner, PF, Busch, CJL, Kane, C, Hübel, K, Dekker, F, Hedberg, C, Rengarajan, B, Drepper, C, Waldmann, H, Kauppinen, S, Greenberg, ME, Draguhn, A, Rehmsmeier, M, Martinez, J & Schratt, GM 2009, 'A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis', Nature Cell Biology, bind 11, nr. 6, s. 705-16. https://doi.org/10.1038/ncb1876

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title = "A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis",

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 = "Gabriele Siegel and Gregor Obernosterer and Roberto Fiore and Martin Oehmen and Silvia Bicker and Mette Christensen and Sharof Khudayberdiev and Leuschner, {Philipp F} and Busch, {Clara J L} and Christina Kane and Katja H{\"u}bel and Frank Dekker and Christian Hedberg and Balamurugan Rengarajan and Carsten Drepper and Herbert Waldmann and Sakari Kauppinen and Greenberg, {Michael E} and Andreas Draguhn and Marc Rehmsmeier and Javier Martinez and Schratt, {Gerhard M}",

note = "Keywords: Animals; Base Sequence; Cell Line; Dendritic Spines; GTP-Binding Protein alpha Subunits, G12-G13; Gene Expression Profiling; Hippocampus; Humans; Lipoylation; Mice; Mice, Inbred C57BL; MicroRNAs; Molecular Sequence Data; Morphogenesis; Neurons; Oligonucleotide Array Sequence Analysis; Rats; Receptors, Glutamate; Synapses; Thiolester Hydrolases",

year = "2009",

doi = "10.1038/ncb1876",

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pages = "705--16",

journal = "Nature Cell Biology",

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T1 - A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis

AU - Siegel, Gabriele

AU - Obernosterer, Gregor

AU - Fiore, Roberto

AU - Oehmen, Martin

AU - Bicker, Silvia

AU - Christensen, Mette

AU - Khudayberdiev, Sharof

AU - Leuschner, Philipp F

AU - Busch, Clara J L

AU - Kane, Christina

AU - Hübel, Katja

AU - Dekker, Frank

AU - Hedberg, Christian

AU - Rengarajan, Balamurugan

AU - Drepper, Carsten

AU - Waldmann, Herbert

AU - Kauppinen, Sakari

AU - Greenberg, Michael E

AU - Draguhn, Andreas

AU - Rehmsmeier, Marc

AU - Martinez, Javier

AU - Schratt, Gerhard M

N1 - Keywords: Animals; Base Sequence; Cell Line; Dendritic Spines; GTP-Binding Protein alpha Subunits, G12-G13; Gene Expression Profiling; Hippocampus; Humans; Lipoylation; Mice; Mice, Inbred C57BL; MicroRNAs; Molecular Sequence Data; Morphogenesis; Neurons; Oligonucleotide Array Sequence Analysis; Rats; Receptors, Glutamate; Synapses; Thiolester Hydrolases

PY - 2009

Y1 - 2009

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.

AB - 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.

U2 - 10.1038/ncb1876

DO - 10.1038/ncb1876

M3 - Journal article

C2 - 19465924

SN - 1465-7392

VL - 11

SP - 705

EP - 716

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 6

ER -