The transport of Staufen2‐containing ribonucleoprotein complexes involves kinesin motor protein and is modulated by mitogen‐activated protein kinase pathway

Abstract

There is increasing evidence showing that mRNA is transported to the neuronal dendrites in ribonucleoprotein (RNP) complexes or RNA granules, which are aggregates of mRNA, rRNA, ribosomal proteins, and RNA-binding proteins. In these RNP complexes, Staufen, a double-stranded RNA-binding protein, is believed to be a core component that plays a key role in the dendritic mRNA transport. This study investigated the molecular mechanisms of the dendritic mRNA transport using green fluorescent protein-tagged Staufen2 produced employing a Sindbis viral expression system. The kinesin heavy chain was found to be associated with Staufen2. The inhibition of kinesin resulted in a significant decrease in the level of dendritic transport of the Staufen2-containing RNP complexes in neurons under non-stimulating or stimulating conditions. This suggests that the dendritic transport of the Staufen2-containing RNP complexes use kinesin as a motor protein. A mitogen-activated protein kinase inhibitor, PD98059, inhibited the activity-induced increase in the amount of both the Staufen2-containing RNP complexes and Ca(2+)/calmodulin-dependent protein kinase II alpha-subunit mRNA in the distal dendrites of cultured hippocampal neurons. Overall, these results suggest that dendritic mRNA transport is mediated via the Staufen2 and kinesin motor proteins and might be modulated by the neuronal activity and mitogen-activated protein kinase pathway.

Genome wide identification of Staufen2-bound mRNAs in embryonic rat brains

“…Stau2 is an RNA-binding protein mainly expressed in different cells of the brain (4, 6) and its importance for mRNA transport in dendrites (5,8) and synaptic functions (10) has been established. RNA transport is a complex process that relies on a highly heterogeneous population of mRNA particles and granules (3).…”

“…However, its role in the post-transcriptional regulation of β-actin and/or other mRNAs in brain cells is not yet clear. Stau2 may influence mRNA transport and/or localization in cellular processes since previous work has implicated Stau2 in dendritic mRNA transport (5,8,9). Alternatively, based on known functions of its paralog Stau1, Stau2 may also control the stability or the translation of specific mRNAs.…”

“…These proteins finely control the successive steps that insure proper expression of mRNA at specific times and space. Staufen2 (Stau2), a protein mainly expressed in brain is a well accepted player for mRNA localization (4)(5)(6)(7)(8)(9). In brain, Stau2 is expressed in several cell types including neurons and oligodendrocytes.…”

BDNF-induced local protein synthesis and synaptic plasticity

“…The Staufen family of proteins comprises two members, Staufen1 and Staufen2, which are components of different RNA granules in neurons (Duchaine et al, 2002). Staufen2 is mainly expressed in the brain and is necessary for the microtubule-dependent delivery of CaMKIIa mRNA to dendrites (Jeong et al, 2007). Staufen1 is required for the late phase of long-term potentiation (L-LTP) in the hippocampus (Lebeau et al, 2008) whereas Staufen2 regulates mGluR-dependent long-term depression (mGluR-LTD) (Lebeau et al, 2011), suggesting distinct roles for the two Staufen proteins at the synapse.…”

Activity-dependent synaptic localization of processing bodies and their role in dendritic structural plasticity

“…The localization of transport RNPs is modulated by synaptic activities, induced by receptor activations, treatment of neurotrophins, or depolarization (Bramham and Wells, 2007). The conventional kinesin (KIF5, kinesin heavy chain) was isolated as the molecular motor of transport RNPs in neurons (Kanai et al, 2004;Hirokawa, 2006;Jeong et al, 2007). P-bodies are also localized near the synaptic regions and their localization is modulated by neuronal activations (Cougot et al, 2008), suggesting an active transport using molecular motors.…”