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

• Published in: The Journal of cell biology Vol. 172; no. 2; pp. 221 - 231
• Main Authors: Goetze, Bernhard, Tuebing, Fabian, Xie, Yunli, Dorostkar, Mario M, Thomas, Sabine, Pehl, Ulrich, Boehm, Stefan, Macchi, Paolo, Kiebler, Michael A
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 16.01.2006; The Rockefeller University Press
• Subjects: Actins; Actins - genetics; Actins - metabolism; Animals; Brain; Brain - metabolism; Cells, Cultured; Cytoskeleton - metabolism; Cytoskeleton - ultrastructure; Dendrites; Dendrites - metabolism; Dendrites - ultrastructure; Dendritic spines; Disks Large Homolog 4 Protein; Down regulation; Excitatory Postsynaptic Potentials - physiology; Gene expression; HeLa Cells; Hippocampus - cytology; Humans; In Situ Hybridization; In Situ Hybridization, Fluorescence; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Messenger RNA; Neurons; Neurons - cytology; Neurons - physiology; Patch-Clamp Techniques; Plasmids; Protein isoforms; Protein Isoforms - genetics; Protein Isoforms - metabolism; Proteins; Rats; Ribonucleic acid; RNA; RNA Interference; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Synapses; Synapses - metabolism
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200509035

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 {szligbeta}-actin mRNA and fewer dendritic {szligbeta}-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.