Cytochalasans and Their Impact on Actin Filament Remodeling

Author:

Lambert Christopher123ORCID,Schmidt Katharina2ORCID,Karger Marius14ORCID,Stadler Marc3ORCID,Stradal Theresia E. B.2ORCID,Rottner Klemens1245ORCID

Affiliation:

1. Molecular Cell Biology Group, Helmholtz Centre for Infection Research (HZI), Inhoffenstrasse 7, 38124 Braunschweig, Germany

2. Department of Cell Biology, Helmholtz Centre for Infection Research (HZI), Inhoffenstrasse 7, 38124 Braunschweig, Germany

3. Department of Microbial Drugs, Helmholtz Centre for Infection Research and German Centre for Infection Research (DZIF), Partner Site Hannover/Braunschweig, Inhoffenstrasse 7, 38124 Braunschweig, Germany

4. Division of Molecular Cell Biology, Zoological Institute, Technische Universität Braunschweig, Spielmannstrasse 7, 38106 Braunschweig, Germany

5. Braunschweig Integrated Centre of Systems Biology (BRICS), 38106 Braunschweig, Germany

Abstract

The eukaryotic actin cytoskeleton comprises the protein itself in its monomeric and filamentous forms, G- and F-actin, as well as multiple interaction partners (actin-binding proteins, ABPs). This gives rise to a temporally and spatially controlled, dynamic network, eliciting a plethora of motility-associated processes. To interfere with the complex inter- and intracellular interactions the actin cytoskeleton confers, small molecular inhibitors have been used, foremost of all to study the relevance of actin filaments and their turnover for various cellular processes. The most prominent inhibitors act by, e.g., sequestering monomers or by interfering with the polymerization of new filaments and the elongation of existing filaments. Among these inhibitors used as tool compounds are the cytochalasans, fungal secondary metabolites known for decades and exploited for their F-actin polymerization inhibitory capabilities. In spite of their application as tool compounds for decades, comprehensive data are lacking that explain (i) how the structural deviances of the more than 400 cytochalasans described to date influence their bioactivity mechanistically and (ii) how the intricate network of ABPs reacts (or adapts) to cytochalasan binding. This review thus aims to summarize the information available concerning the structural features of cytochalasans and their influence on the described activities on cell morphology and actin cytoskeleton organization in eukaryotic cells.

Funder

Life-Science Foundation

German Research Council through the CytoLabs consortium

Publisher

MDPI AG

Subject

Molecular Biology,Biochemistry

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