Abstract
BackgroundDendritic spines are small membranous protrusions on the neuronal dendrites that receive synaptic input from axon terminals. Despite their importance for integrating the enormous information flow in the brain, the molecular mechanisms regulating spine morphogenesis are not well understood. NESH/Abi-3 is a member of the Abl interactor (Abi) protein family, and its overexpression is known to reduce cell motility and tumor metastasis. NESH is prominently expressed in the brain, but its function there remains unknown.Methodology/Principal FindingsNESH was strongly expressed in the hippocampus and moderately expressed in the cerebral cortex, cerebellum and striatum, where it co-localized with the postsynaptic proteins PSD95, SPIN90 and F-actin in dendritic spines. Overexpression of NESH reduced numbers of mushroom-type spines and synapse density but increased thin, filopodia-like spines and had no effect on spine density. siRNA knockdown of NESH also reduced mushroom spine numbers and inhibited synapse formation but it increased spine density. The N-terminal region of NESH co-sedimented with filamentous actin (F-actin), which is an essential component of dendritic spines, suggesting this interaction is important for the maturation of dendritic spines.Conclusions/SignificanceNESH is a novel F-actin binding protein that likely plays important roles in the regulation of dendritic spine morphogenesis and synapse formation.
Highlights
Most excitatory synapses in brain are formed at tiny dendritic protrusions called dendritic spines
We found that NESH expression gradually increased during development and exhibited a pattern similar to those seen with three other postsynaptic proteins, SPIN90, Homer1c and PSD95 (Fig. 1A)
The immunoblot analysis showed that NESH was most abundant in the hippocampus but was moderately expressed in the cerebral cortex, cerebellum and striatum; it was rarely seen in the other brain regions (Fig. 1B)
Summary
Most excitatory synapses in brain are formed at tiny dendritic protrusions called dendritic spines. It is believed that the brain stores information in part by modulating the strength of existing synapses, and by enlarging or shrinking dendritic spines, which leads to the formation or elimination of synapses These functional and structural changes in dendritic spines are thought to be the basis of learning and memory in the brain [4,5]. Dendritic spines are small membranous protrusions on the neuronal dendrites that receive synaptic input from axon terminals Despite their importance for integrating the enormous information flow in the brain, the molecular mechanisms regulating spine morphogenesis are not well understood. NESH is prominently expressed in the brain, but its function there remains unknown
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