The role of drebrin in neurons

Abstract

Drebrin is an actin-binding protein that changes the helical pitch of actin filaments (F-actin), and drebrin-decorated F-actin shows slow treadmilling and decreased rate of depolymerization. Moreover, the characteristic morphology of drebrindecorated F-actin enables it to respond differently to the same signals from other actin cytoskeletons. Drebrin consists of two major isoforms, drebrin E and drebrin A. In the developing brain, drebrin E appears in migrating neurons and accumulates in the growth cones of axons and dendrites. Drebrin E-decorated Factin links lamellipodium F-actin to microtubules in the growth cones. Then drebrin A appears at nascent synapses and drebrin A-decorated F-actin facilitates postsynaptic molecular assembly. In the adult brain, drebrin A-decorated F-actin is concentrated in the central region of dendritic spines. During long-term potentiation initiation, NMDA receptor-mediated Ca 2+ influx induces the transient exodus of drebrin A-decorated F-actin via myosin II ATPase activation. Because of the unique physical characteristics of drebrin A-decorated F-actin, this exodus likely contributes to the facilitation of F-actin polymerization and spine enlargement. Additionally, drebrin reaccumulation in dendritic spines is observed after the exodus. In our drebrin exodus model of structure-based synaptic plasticity, reestablishment of drebrin A-decorated F-actin is necessary to keep the enlarged spine size during long-term potentiation maintenance. In this review, we introduce the genetic and biochemical properties of drebrin and the roles of drebrin in early stage of brain development, synaptic formation and synaptic plasticity. Further, we discuss the pathological relevance of drebrin loss in Alzheimer's disease.

Plasticity of Spine Structure: Local Signaling, Translation and Cytoskeletal Reorganization

“…For formation and stabilization of complex actin networks, cross-linking proteins such as drebrin, α-actinin and Calcium/calmodulin-dependent protein kinase type II subunit β (CaMKIIβ) play a key role for bundling F-actin (Hotulainen and Hoogenraad, 2010; Kim et al, 2015). The transient exit and reentry of drebrin A in the spine head is thought to be important for spine remodeling (Bosch et al, 2014; Mizui et al, 2014; Shirao et al, 2017). In addition, myosin, a superfamily of ATP-driven motor proteins, regulates spine structure via its multiple functions including protein trafficking and contractile bundling of F-actin networks (Ryu et al, 2006; Correia et al, 2008; Wang Z. et al, 2008; Korobova and Svitkina, 2010).…”

Mechanisms of neuronal migration in the adult brain

“…; Sonego et al . , ) (Drebrin's function is reviewed in this issue: Shirao et al ., ), suggesting that the regulation of actin polymerization by these factors is required for proper formation and extension of the leading process.…”

“…Rac1 and Vav3, a guanine nucleotide exchange factor that can activate Rac1, are required for neuronal migration toward the olfactory bulb (Khodosevich et al 2009). Vav3 knockdown disrupts the actin-rich growth cone at the tip of the leading process, and deleting one of the actin-binding proteins Drebrin or Fascin causes the shaft of the process to branch abnormally in migrating neuroblasts (Song et al 2008;Sonego et al 2013Sonego et al , 2015 (Drebrin's function is reviewed in this issue: Shirao et al, 2017), suggesting that the regulation of actin polymerization by these factors is required for proper formation and extension of the leading process.…”

60th Anniversary of the Japanese Society for Neurochemistry

“…Tomoaki Shirao and his colleagues discovered drebrin, and their passionate research over the past three decades has elucidated vital roles of a neuron‐specific drebrin isoform in the postsynaptic formation and synaptic plasticity (Shirao et al . ). Drebrin is now energetically studied worldwide across various disciplines.…”

“…The Drebrin, an actin-binding protein, alters the morphology and mechanical properties of actin filaments and creates a unique platform for molecular assembly in intercellular communication. Tomoaki Shirao and his colleagues discovered drebrin, and their passionate research over the past three decades has elucidated vital roles of a neuron-specific drebrin isoform in the postsynaptic formation and synaptic plasticity (Shirao et al 2017). Drebrin is now energetically studied worldwide across various disciplines.…”