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Vol. 19, Issue 5, 2311-2327, May 2008

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

Yuanzheng Gao^*,, Vedakumar Tatavarty^*,, George Korza, Mikhail K. Levin^,, and John H. Carson^,

*Neuroscience Program, Department of Molecular Microbial and Structural Biology; Richard Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington CT 06030

Submitted September 18, 2007; Revised January 2, 2008; Accepted February 19, 2008
Monitoring Editor: Karsten Weis

In neurons, many different RNAs are targeted to dendrites where local expression of the encoded proteins mediates synaptic plasticity during learning and memory. It is not known whether each RNA follows a separate trafficking pathway or whether multiple RNAs are targeted to dendrites by the same pathway. Here, we show that RNAs encoding calcium calmodulin-dependent protein kinase II, neurogranin, and activity-regulated cytoskeleton-associated protein are coassembled into the same RNA granules and targeted to dendrites by the same cis/trans-determinants (heterogeneous nuclear ribonucleoprotein [hnRNP] A2 response element and hnRNP A2) that mediate dendritic targeting of myelin basic protein RNA by the A2 pathway in oligodendrocytes. Multiplexed dendritic targeting of different RNAs by the same pathway represents a new organizing principle for coordinating gene expression at the synapse.

These authors contributed equally to this work.

Address correspondence to: John H. Carson (jcarson{at}nso2.uchc.edu)

Abbreviations used: A2RE, hnRNP A2 response element; ARC, activity-regulated cytoskeleton-associated protein; CaMKII, calcium calmodulin-dependent protein kinase II; demux, demultiplexer; FBS, fetal bovine serum; FCCS, fluorescent cross-correlation spectroscopy; FISH, fluorescent in situ hybridization; HBSS, Hank's balanced salt solution; hnRNP, heterogeneous nuclear ribonucleoprotein; mux, multiplexer; NG, neurogranin; PKM, protein kinase M; SPR, surface plasmon resonance.