Abstract
BackgroundEpidermal growth factor receptor substrate 8 (Eps8) is a multifunctional protein that regulates actin cytoskeleton dynamics and architecture through its barbed-end capping and bundling activities. In cultured hippocampal neurons, Eps8 is enriched at dendritic spine heads and is required for spine morphogenesis; however, the detailed expression pattern of Eps8 in the hippocampus has not yet been explored.ResultsHere, we demonstrate that endogenous Eps8 protein is restrictively expressed in neurons (NeuN-positive), but not in glial cells (glial fibrillary acidic protein-positive) in area CA1 of the mouse hippocampus. Surprisingly, Eps8 immunoreactivity is rarely found in pyramidal cell somata, but is expressed predominantly in the somata and dendrites of 67 kDa isoform of glutamic acid decarboxylase-expressing GABAergic interneurons in the stratum radiatum and at the border of stratum radiatum and lacunosum-moleculare of area CA1. On the basis of co-localizing markers, we found that Eps8 is not present in perisomatic inhibitory parvalbumin-expressing cells or calretinin-expressing interneurons. However, Eps8 is richly expressed in calbindin-expressing interneurons. Furthermore, Eps8 is also present in cholecystokinin-expressing interneurons, but not in somatostatin-expressing interneurons in area CA1 stratum pyramidale and stratum radiatum.ConclusionsThese results reveal a previously unknown cell type-specific expression pattern of endogenous Eps8 protein in the mouse hippocampus and speculate that the role of Eps8 in controlling and orchestrating neuronal morphogenesis and structural plasticity might be more prominent in interneurons than in pyramidal cells of the hippocampus.
Highlights
Epidermal growth factor receptor substrate 8 (Eps8) is a multifunctional protein that regulates actin cytoskeleton dynamics and architecture through its barbed-end capping and bundling activities
Recent studies show that Eps8 contributes to the formation of dendritic spines and activity-mediated synaptic plasticity in cultured hippocampal neuron model [9] and Eps8-null mice exhibits a defect in spine formation and learning-dependent spinogenesis in the hippocampus [10]
Our data suggest that Eps8 protein in the hippocampus is predominantly expressed in calbindin- and cholecystokinin-expressing GABAergic interneurons in area CA1 stratum radiatum and the border of lacunosum-moleculare
Summary
Epidermal growth factor receptor substrate 8 (Eps8) is a multifunctional protein that regulates actin cytoskeleton dynamics and architecture through its barbed-end capping and bundling activities. Previous structural and functional studies have revealed that Eps, via its SH3 domain, participates in forming distinct protein complexes that either transduce signals from Ras to Rac leading to actin remodeling or regulate endocytosis of receptor tyrosine kinases [2,3,4]. Eps has been shown to regulate axonal filopodia formation in cultured hippocampal neurons in response to brain-derived neurotrophic factor [11]. These results strongly suggest an important role for Eps in the regulation of hippocampal neuronal structure and function. Our data suggest that Eps protein in the hippocampus is predominantly expressed in calbindin- and cholecystokinin-expressing GABAergic interneurons in area CA1 stratum radiatum and the border of lacunosum-moleculare
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