Microscopic studies on severing properties of actin-binding protein: its potential use in therapeutic treatment of actin-rich inclusions

Han-Ul Kim,Jeong Min Chung,Hyun Suk Jung,Dooil Jeoung,Anahita Vispi Bharda,Jeong Chan Moon

doi:10.1186/s40543-021-00305-2

Abstract

Actin is an important unit of the cytoskeletal system, involved in many cellular processes including cell motility, signaling, and intracellular trafficking. Various studies have been undertaken to understand the regulatory mechanisms pertaining actin functions, especially the ones controlled by actin-binding proteins. However, not much has been explored about the molecular aspects of these proteins implicated in various diseases. In this study, we aimed to demonstrate the molecular properties of gelsolin, an actin-severing protein on the disassembly of the aggregation of actin-rich intracellular inclusions, Hirano body. We observed a decreasing tendency of actin aggregation by co-sedimentation assay and transmission electron microscopy in the presence of gelsolin. Therefore, we provide suggestive evidence for the use of actin-severing protein in novel therapeutic strategies for neurodegenerative conditions.

Highlights

Actin is a fundamental cytoskeletal protein abundantly found in most eukaryotic cells
We demonstrated the potential application of actin-severing protein, gelsolin on actin-rich intracellular inclusions Hirano body by co-sedimentation assay and Transmission electron microscopy (TEM)
Stained electron micrographs were analyzed to understand the activity of actin in the presence of Ca2+ with or without Actinbinding protein (ABP) such as ABP34 and Gelsolin

Summary

Introduction

Actin is a fundamental cytoskeletal protein abundantly found in most eukaryotic cells. Recent studies have shown its critical role in several conditions including amyloidosis, inflammation, cardiovascular diseases and cancer (Spinardi and Witke 2007). Another class of actin-binding protein, ABP34 is a small, 34 kDa crosslinking protein organizing F-actin into condensed bundles in a calcium dependent manner (Lim et al 1999). Eosinophilic, actin-rich intracytoplasmic structures that contain paracrystalline arrays of F-actin (Goldman 1983) and ABPs (Galloway et al 1987). We used gelsolin to compete with enormous bundled actin filaments for resolving the phenomenon of actin aggregation

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