Shank1 mRNA: dendritic transport by kinesin and translational control by the 5'untranslated region.
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.
Falley
Katrin
K
Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf; Martinistrasse 52; 20246 Hamburg, Germany.
Schütt
Janin
J
Iglauer
Peter
P
Menke
Katharina
K
Maas
Christoph
C
Kneussel
Matthias
M
Kindler
Stefan
S
Wouters
Fred S
FS
Richter
Dietmar
D
Kreienkamp
Hans-Jürgen
HJ
D020121:5' Untranslated Regions; D001692:Biological Transport / Q000502:physiology; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D020121:5' Untranslated Regions; C507512:Kif5A protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C512412:SHANK1 protein, mouse; C492187:Stau1 protein, mouse; D016547:Kinesins