Multiplexed Dendritic Targeting of α Calcium Calmodulin-dependent Protein Kinase II, Neurogranin, and Activity-regulated Cytoskeleton-associated Protein RNAs by the A2 Pathway

BDNF-induced local protein synthesis and synaptic plasticity

“…However, additional studies showed that CaMKIIa mRNA containing this element but lacking most of the 3 0 UTR fail to be targeted to dendrites in vivo (Miller et al, 2002). Furthermore, another localization element was identified in the middle of the 3 0 UTR of CaMKIIa transcript (Blichenberg et al, 2001), and the CaMKIIa transcript also contains a hnRNPA2 response element (A2RE) (Gao et al, 2008). Taken together, these findings suggest that the dendritic localization of CaMKIIa mRNA depends on diverse cis-acting elements.…”

“…Taken together, these findings suggest that the dendritic localization of CaMKIIa mRNA depends on diverse cis-acting elements. Similarly, two different localization elements were described for the Arc mRNA (Gao et al, 2008;Kobayashi et al, 2005) but surprisingly little is known about the mechanism of Arc mRNA transport into dendrites. In hippocampal neurons the Arc transcripts are transported along dendrites in hnRNPA2-containing granules (Gao et al, 2008) and a cis-acting element on the 3 0 UTR of the Arc mRNA showed a moderate ability to target these transcripts to dendrites (Kobayashi et al, 2005).…”

“…This element is called heterogeneous nuclear ribonucleoprotein (hnRNP) A2 response element (A2RE) because it is recognized by hnRNPA2, a trans-acting factor responsible for MBP mRNA trafficking in oligodendrocytes (Munro et al, 1999). The A2RE-dependent targeting of mRNAs is also involved in the dendritic delivery of Arc, CaMKIIa, and Neurogranin mRNAs, which appear to cluster in the same hnRNPA2-containing granules (Gao et al, 2008). Moreover, hnRNPA2 was also shown to be necessary for the delivery of the non-coding BC1 RNA and PKMz mRNA to distal dendritic domains (Muslimov et al, 2006(Muslimov et al, , 2011.…”

mRNP granules

“…23 Staining with in situ probes against common leader sequence or poly-adenylated mRNAs also suggest a large population of mRNAs reside in germ granules, 92,93 as well as Pbodies and stress granules. 24,25 Approaches using specific mRNA labeling also shows co-migration of several mRNA species in neuronal granule subtypes, 95 and the Ash1 locasome in yeast, 96,97 and many mRNA species individually localize in stress granules or Pbodies under identical conditions. 98,99 In contrast, recent quantitative imaging approaches in neurons indicates that some mRNA species can transit in granules or "particles" harboring just a single mRNA molecule.…”

“…Supporting this, several mRNAs harboring identical cis regulatory elements can co-localize in particular transport granules. 95,103 This might allow bursts of synthesis of several proteins with related function to locally respond to rapid signals that occurs at neuronal synapses. Grouping mRNPs in a single particle might also be more energy efficient in that fewer interactions with factors mediating transport (e.g., motor proteins) may be necessary, and maintenance of mRNPs in a repressed state might be facilitated by a higher local concentration of repressor proteins.…”