Determination of dendritic spine morphology by the striatin scaffold protein STRN4 through interaction with the phosphatase PP2A

Abstract

Most excitatory synapses are located in dendritic spines of the postsynaptic neuron. Mature spines appear as mushroom-shaped with large heads, whereas, immature spines include stubby spines or filopodia, which do not possess a distinct spine head, and thin spines which contain elongated necks and small heads. Spine maturation requires local dendritic protein synthesis and spontaneous activity of N-methyl-D-aspartate (NMDA) receptor. Dysregulated mRNA trafficking and local protein synthesis can lead to altered spine morphology in neurodevelopmental disorders such as Fragile-X syndrome and autism. How different subtypes of dendritic spines are selectively maintained along development is still poorly understood. strn4 was identified in recent transcriptomic studies as an mRNA transcript present in hippocampal neuropil and putative cargo of the RNA-binding protein FMRP. STRN4 belongs to the striatin family of scaffold proteins, and some of the potential striatin-interacting proteins are encoded by autism risk genes. Although previous studies have demonstrated their localization in dendritic spines, the function of various striatin family members in neuron remains unknown. Here we demonstrate that strn4 mRNA is present in neuronal dendrites and the local expression of STRN4 protein depends on NMDA receptor activation. Notably, STRN4 is preferentially expressed in mushroom spines, and STRN4 specifically maintains mushroom spines but not thin spines and filopodia through interaction with the phosphatase PP2A. Our findings have therefore unraveled the local expression of STRN4 as a novel mechanism for the control of dendritic spine morphology.