Mammalian Staufen2 (Stau2) is a member of the double-stranded RNA-binding protein family. Its expression is largely restricted to the brain. It is thought to play a role in the delivery of RNA to dendrites of polarized neurons. To investigate the function of Stau2 in mature neurons, we interfered with Stau2 expression by RNA interference (RNAi). Mature neurons lacking Stau2 displayed a significant reduction in the number of dendritic spines and an increase in filopodia-like structures. The number of PSD95-positive synapses and miniature excitatory postsynaptic currents were markedly reduced in Stau2 down-regulated neurons. Akin effects were caused by overexpression of dominant-negative Stau2. The observed phenotype could be rescued by overexpression of two RNAi cleavage-resistant Stau2 isoforms. In situ hybridization revealed reduced expression levels of β-actin mRNA and fewer dendritic β-actin mRNPs in Stau2 down-regulated neurons. Thus, our data suggest an important role for Stau2 in the formation and maintenance of dendritic spines of hippocampal neurons.
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16 January 2006
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January 17 2006
The brain-specific double-stranded RNA-binding protein Staufen2 is required for dendritic spine morphogenesis
Bernhard Goetze,
Bernhard Goetze
1Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany
2Center for Brain Research
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Fabian Tuebing,
Fabian Tuebing
1Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany
2Center for Brain Research
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Yunli Xie,
Yunli Xie
1Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany
2Center for Brain Research
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Mario M. Dorostkar,
Mario M. Dorostkar
3Institute for Pharmacology, Medical University of Vienna, A-1090 Vienna, Austria
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Sabine Thomas,
Sabine Thomas
1Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany
2Center for Brain Research
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Ulrich Pehl,
Ulrich Pehl
4Department of Drug Discovery Support, General Pharmacology Group, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach, Germany
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Stefan Boehm,
Stefan Boehm
3Institute for Pharmacology, Medical University of Vienna, A-1090 Vienna, Austria
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Paolo Macchi,
Paolo Macchi
1Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany
2Center for Brain Research
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Michael A. Kiebler
Michael A. Kiebler
1Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany
2Center for Brain Research
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Bernhard Goetze
1Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany
2Center for Brain Research
Fabian Tuebing
1Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany
2Center for Brain Research
Yunli Xie
1Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany
2Center for Brain Research
Mario M. Dorostkar
3Institute for Pharmacology, Medical University of Vienna, A-1090 Vienna, Austria
Sabine Thomas
1Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany
2Center for Brain Research
Ulrich Pehl
4Department of Drug Discovery Support, General Pharmacology Group, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach, Germany
Stefan Boehm
3Institute for Pharmacology, Medical University of Vienna, A-1090 Vienna, Austria
Paolo Macchi
1Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany
2Center for Brain Research
Michael A. Kiebler
1Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany
2Center for Brain Research
Correspondence to: [email protected]
Abbreviations used in this paper: DIV, days in vitro; FMRP, Fragile X mental retardation protein; mEPSC, miniature excitatory postsynaptic current; RNAi, RNA interference; shRNA, short hairpin RNA; siRNA, small interfering RNA; TLS, translocated in liposarcoma.
Received:
September 06 2005
Accepted:
December 16 2005
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2006
J Cell Biol (2006) 172 (2): 221–231.
Article history
Received:
September 06 2005
Accepted:
December 16 2005
Citation
Bernhard Goetze, Fabian Tuebing, Yunli Xie, Mario M. Dorostkar, Sabine Thomas, Ulrich Pehl, Stefan Boehm, Paolo Macchi, Michael A. Kiebler; The brain-specific double-stranded RNA-binding protein Staufen2 is required for dendritic spine morphogenesis . J Cell Biol 16 January 2006; 172 (2): 221–231. doi: https://doi.org/10.1083/jcb.200509035
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