Abstract
Drebrin is an actin bundling protein that plays critical roles in synaptic spine development and plasticity. Homer, one of the most abundant scaffolding proteins in postsynaptic density, interacts with Drebrin's C-terminal PPXXF motifs using its Ena/VASP homology 1 (EVH1) domain. However, the molecular mechanism and biological function of this interaction remain unclear. Here we show that Homer specifically binds to the first but not the second PPXXF motif in Drebrin. The crystal structure of Drebrin-Homer binding motif 1 in complex with Homer EVH1 reveals a consensus Homer EVH1 binding motif. Homer tetramer promotes actin bundling activity of Drebrin invitro and stimulates Drebrin-induced filopodia formation and elongation in cells. We further show that monomeric Homer1a antagonizes Homer1b in promoting Drebrin-stimulated actin bundling. Our study suggests a potential regulatory role of Homer1 in modulating excitatory synaptic spine homeostatic scaling via binding to Drebrin.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
