A loss of function allele for murine Staufen1 leads to impairment of dendritic Staufen1-RNP delivery and dendritic spine morphogenesis

John P Vessey; Paolo Macchi; Joel M Stein; Martin Mikl; Kelvin N Hawker; Petra Vogelsang; Krzysztof Wieczorek; Georgia Vendra; Julia Riefler; Fabian Tübing; Samuel A. J Aparicio; Ted Abel; Michael A Kiebler

doi:10.1073/pnas.0804583105

Back

A loss of function allele for murine Staufen1 leads to impairment of dendritic Staufen1-RNP delivery and dendritic spine morphogenesis

Journal article

Open access

Peer reviewed

A loss of function allele for murine Staufen1 leads to impairment of dendritic Staufen1-RNP delivery and dendritic spine morphogenesis

John P Vessey, Paolo Macchi, Joel M Stein, Martin Mikl, Kelvin N Hawker, Petra Vogelsang, Krzysztof Wieczorek, Georgia Vendra, Julia Riefler, Fabian Tübing, …

Proceedings of the National Academy of Sciences - PNAS, Vol.105(42), pp.16374-16379

10/21/2008

DOI: 10.1073/pnas.0804583105

PMCID: PMC2567905

PMID: 18922781

Files and links (1)

url

https://doi.org/10.1073/pnas.0804583105View

Published (Version of record) Open Access

Abstract

The dsRNA-binding protein Staufen was the first RNA-binding protein proven to play a role in RNA localization in Drosophila . A mammalian homolog, Staufen1 (Stau1), has been implicated in dendritic RNA localization in neurons, translational control, and mRNA decay. However, the precise mechanisms by which it fulfills these specific roles are only partially understood. To determine its physiological functions, the murine Stau1 gene was disrupted by homologous recombination. Homozygous stau1 tm1Apa mutant mice express a truncated Stau1 protein lacking the functional RNA-binding domain 3. The level of the truncated protein is significantly reduced. Cultured hippocampal neurons derived from stau1 tm1Apa homozygous mice display deficits in dendritic delivery of Stau1-EYFP and β- actin mRNA-containing ribonucleoprotein particles (RNPs). Furthermore, these neurons have a significantly reduced dendritic tree and develop fewer synapses. Homozygous stau1 tm1Apa mutant mice are viable and show no obvious deficits in development, fertility, health, overall brain morphology, and a variety of behavioral assays, e.g., hippocampus-dependent learning. However, we did detect deficits in locomotor activity. Our data suggest that Stau1 is crucial for synapse development in vitro but not critical for normal behavioral function.

Biological Sciences

dendrite

double-stranded RNA-binding protein

RNA transport

ribonucleoprotein particles

Details

Title: Subtitle: A loss of function allele for murine Staufen1 leads to impairment of dendritic Staufen1-RNP delivery and dendritic spine morphogenesis
Creators: John P Vessey - The-Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076, Tübingen, Germany
Paolo Macchi - The-Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076, Tübingen, Germany
Joel M Stein - Department of Biology, University of Pennsylvania, Philadelphia, PA 19104; and
Martin Mikl - Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria
Kelvin N Hawker - Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Department of Oncology, Hills Road, Cambridge, CB2 2XY, United Kingdom
Petra Vogelsang - The-Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076, Tübingen, Germany
Krzysztof Wieczorek - Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria
Georgia Vendra - Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria
Julia Riefler - Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria
Fabian Tübing - The-Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076, Tübingen, Germany
Samuel A. J Aparicio - Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Department of Oncology, Hills Road, Cambridge, CB2 2XY, United Kingdom
Ted Abel - Department of Biology, University of Pennsylvania, Philadelphia, PA 19104; and
Michael A Kiebler - The-Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076, Tübingen, Germany
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.105(42), pp.16374-16379
DOI: 10.1073/pnas.0804583105
PMID: 18922781
PMCID: PMC2567905
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 10/21/2008
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065732702771

Metrics

29 Record Views

95 Times Cited - Web of Science