Staufen 2 regulates mGluR long-Term depression and Mapth mRNA distribution in hippocampal neurons

Abstract

The two members of the Staufen family of RNA-binding proteins, Staul and Stau2, are present in distinct ribonudeoprotein complexes and associate with different mRNAs. Staul is required for protein synthesis-dependent long-Term potentiation (L-LTP) in hippocanipal pyraniidal cells. However, the role of Srau2 in synaptic plasticity reniains unexplored. We found that unlike Staul, Stau2 is not required for 1-UP. In contrast, Stau2, but not Staul, is necessary for DHPG-induced protein synthesis-dependent long-Term depression (mGluR-IJDJ. While Stau2 is involved iii early development of spines, its down-regulation does not alter spine morphology or spontaneous miniature synaptic activity in older cultures where LTD occurs. In addition, Stau2, but not Staul, knockdown reduces the dendritic localization of Mapib mR.NA, a specific transcript involved in mGluR-LTD. Moreover, mGluR stimulation with DHPG induces Mapib, but not Map2, niRNA dissociation from niRNA granules containing Stau2 and the ribosomal protein P0. This dissociation was not observed in cells in which Stau2 was depleted. Finally, Stau2 knockdown reduces basal Mapib protein expression in dendrites and prevents DHPG-induced increases in dendritic Mapib protein level. We suggest a role for Stau2 in the generation and regulation of Mapib mRNA containing granules that are required for mGluR-UJD.