Shank1 mRNA: dendritic transport by kinesin and translational control by the 5'untranslated region.

Authors: Falley, Katrin  Schütt, Janin  Iglauer, Peter  Menke, Katharina  Maas, Christoph  Kneussel, Matthias  Kindler, Stefan  Wouters, Fred S  Richter, Dietmar  Kreienkamp, Hans-Jürgen 
Citation: Falley K, etal., Traffic. 2009 Jul;10(7):844-57. doi: 10.1111/j.1600-0854.2009.00912.x. Epub 2009 Apr 11.
Pubmed: (View Article at PubMed) PMID:19416473
DOI: Full-text: DOI:10.1111/j.1600-0854.2009.00912.x

Dendritic mRNA transport coupled with local regulation of translation enables neurons to selectively alter the protein composition of individual postsynaptic sites. We have analyzed dendritic localization of shank1 mRNAs; shank proteins (shank1-3) are scaffolding molecules of the postsynaptic density (PSD) of excitatory synapses, which are crucial for PSD assembly and the formation of dendritic spines. Live cell imaging demonstrates saltatory movements of shank1 mRNA containing granules along microtubules in both anterograde and retrograde directions. A population of brain messenger ribonucleoprotein particles (mRNPs) containing shank1 mRNAs associates with the cargo-binding domain of the motor protein KIF5C. Through expression of dominant negative proteins, we show that dendritic targeting of shank1 mRNA granules involves KIF5C and the KIF5-associated RNA-binding protein staufen1. While transport of shank1 mRNAs follows principles previously outlined for other dendritic transcripts, shank1 mRNAs are distinguished by their translational regulation. Translation is strongly inhibited by a GC-rich 5(')untranslated region; in addition, internal ribosomal entry sites previously detected in other dendritic transcripts are absent in the shank1 mRNA. A concept emerges from our data in which dendritic transport of different mRNAs occurs collectively via a staufen1- and KIF5-dependent pathway, whereas their local translation is controlled individually by unique cis-acting elements.


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CRRD Object Information
CRRD ID: 12050142
Created: 2017-01-21
Species: All species
Last Modified: 2017-01-21
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.