Homer Tetramer Promotes Actin Bundling Activity of Drebrin

Zhiwei Li; Haiyang Liu; Jianchao Li; Qingqing Yang; Zhe Feng; Yujie Li; Haibin Yang; Cong Yu; Jun Wan; Wei Liu; Mingjie Zhang

doi:10.1016/j.str.2018.10.011

Homer Tetramer Promotes Actin Bundling Activity of Drebrin

Structure. 2019 Jan 2;27(1):27-38.e4. doi: 10.1016/j.str.2018.10.011. Epub 2018 Nov 29.

Authors

Zhiwei Li¹, Haiyang Liu², Jianchao Li³, Qingqing Yang¹, Zhe Feng³, Yujie Li⁴, Haibin Yang⁴, Cong Yu⁴, Jun Wan², Wei Liu⁵, Mingjie Zhang⁶

Affiliations

¹ Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China.
² Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China; Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
³ Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
⁴ Department of Biology, Southern University of Science and Technology, Shenzhen 518055, China.
⁵ Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China. Electronic address: liuwei@sphmc.org.
⁶ Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China; Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address: mzhang@ust.hk.

PMID: 30503778
DOI: 10.1016/j.str.2018.10.011

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 in vitro 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.

Keywords: Drebrin; EVH1 domain; Homer1; actin bundle; postsynaptic density; proline rich motif; scaffold proteins; synaptic plasticity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / metabolism*
Animals
Binding Sites
COS Cells
Chlorocebus aethiops
Crystallography, X-Ray
Homer Scaffolding Proteins / chemistry*
Homer Scaffolding Proteins / metabolism*
Humans
Mice
Models, Molecular
Neuropeptides / chemistry*
Neuropeptides / metabolism*
Protein Binding
Protein Multimerization

Substances

Actins
Homer Scaffolding Proteins
Neuropeptides
drebrins