The Polyadenosine RNA-Binding Protein ZC3H14 Localizes to Synapses and Regulates Synaptosomal CaMKIIα Levels

Abstract

ZC3H14 (Zinc finger CysCysCysHis domain-containing protein 14), an evolutionarily conserved member of a class of tandem zinc finger (CCCH) polyadenosine (polyA) RNA binding proteins, is associated with a form of heritable, nonsyndromic autosomal recessive intellectual disability. Previous studies of a loss of function mouse model, Zc3h14{Delta}ex13/{Delta}ex13, provide evidence that ZC3H14 is essential for proper brain function, specifically for working memory. To expand on these findings, we analyzed the dendritic spines of hippocampal neurons from Zc3h14{Delta}ex13/{Delta}ex13 mice. These studies reveal that loss of ZC3H14 does not affect dendritic spine density in either CA1 pyramidal neurons or dentate gyrus granule cells in the hippocampus. However, overexpression of ZC3H14 in cultured hippocampal neurons increases the overall density of spines. We next performed biochemical analyses of synaptosomes prepared from whole wild-type and Zc3h14{Delta}ex13/{Delta}ex13 mouse brains to determine if there are changes in steady state levels of postsynaptic proteins upon the loss of ZC3H14. We found that ZC3H14 is present within synaptosomes and that a crucial postsynaptic protein, CaMKII, is significantly increased in these synaptosomal fractions upon loss of ZC3H14. Together, these results demonstrate that ZC3H14 localizes to synapses, that its levels influence dendritic spine morphology, and that its loss dysregulates synaptic CaMKII levels, suggesting a potential role for ZC3H14 in synaptic function and plasticity.