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Published 17 January 2006. doi:10.1083/jcb.200509035
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 2, 221-231
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Article

 The brain-specific double-stranded RNA-binding protein Staufen2 is required for dendritic spine morphogenesis

Bernhard Goetze1,2, Fabian Tuebing1,2, Yunli Xie1,2, Mario M. Dorostkar3, Sabine Thomas1,2, Ulrich Pehl4, Stefan Boehm3, Paolo Macchi1,2, and Michael A. Kiebler1,2

1 Max-Planck-Institute for Developmental Biology, 72076 Tübingen, Germany
2 Center for Brain Research and 3 Institute for Pharmacology, Medical University of Vienna, A-1090 Vienna, Austria
4 Department of Drug Discovery Support, General Pharmacology Group, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach, Germany

Correspondence to: paolo.macchi{at}meduniwien.ac.at

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 ß-actin mRNA and fewer dendritic ß-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.

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.


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