Liprin-α-Mediated Assemblies and Their Roles in Synapse Formation.

Xingqiao Xie,Zhiyi Wei,Cong Yu,Mingfu Liang

doi:10.3389/fcell.2021.653381

Abstract

Brain’s functions, such as memory and learning, rely on synapses that are highly specialized cellular junctions connecting neurons. Functional synapses orchestrate the assembly of ion channels, receptors, enzymes, and scaffold proteins in both pre- and post-synapse. Liprin-α proteins are master scaffolds in synapses and coordinate various synaptic proteins to assemble large protein complexes. The functions of liprin-αs in synapse formation have been largely uncovered by genetic studies in diverse model systems. Recently, emerging structural and biochemical studies on liprin-α proteins and their binding partners begin to unveil the molecular basis of the synaptic assembly. This review summarizes the recent structural findings on liprin-αs, proposes the assembly mechanism of liprin-α-mediated complexes, and discusses the liprin-α-organized assemblies in the regulation of synapse formation and function.

Highlights

In the brain, neurons are connected and communicated with each other via highly specialized intercellular junctions, termed synapses
Recent studies showed that liprin-α proteins undergo either phosphorylation-dependent phase transition or co-phase separation with ELKS (EmperadorMelero et al, 2020; Liang et al, 2020; McDonald et al, 2020). These findings indicate that the self-assembled liprinαs act as a hub to dynamically recruit ELKS, RIM, and other binding partners to form the electron-dense protein aggregates in the presynaptic active zone observed by electron microscopy (Fouquet et al, 2009; Kittelmann et al, 2013; Spangler et al, 2013)
In addition to the promoting effect on LAR clustering (Xie et al, 2020) and the ELKS condensate formation in presynpase maturation (Liang et al, 2020; McDonald et al, 2020), liprin-αs are involved in several other protein assemblies in the synapse (Figure 5B)

Summary

Introduction

Neurons are connected and communicated with each other via highly specialized intercellular junctions, termed synapses. The SAM123 region of liprin-αs have been reported to mediate a diverse array of interactions with kinases (CASK and CAMKII), phosphatases (LAR-RPTPs), and other scaffolds (liprin-β1/2, mSYD1 and RSY-1) in spine formation and presynaptic assembly (Kaufmann et al, 2002; Olsen et al, 2005; Hoogenraad et al, 2007; Patel and Shen, 2009; Wentzel et al, 2013) (Table 1).

Results

Conclusion