Specialization of actin isoforms derived from the loss of key interactions with regulatory factors.

Autor: Boiero Sanders, Micaela, Toret, Christopher P, Guillotin, Audrey, Antkowiak, Adrien, Vannier, Thomas, Robinson, Robert C, Michelot, Alphée
Předmět:
Zdroj: EMBO Journal; Mar2022, Vol. 41 Issue 5, p1-22, 22p
Abstrakt: A paradox of eukaryotic cells is that while some species assemble a complex actin cytoskeleton from a single ortholog, other species utilize a greater diversity of actin isoforms. The physiological consequences of using different actin isoforms, and the molecular mechanisms by which highly conserved actin isoforms are segregated into distinct networks, are poorly known. Here, we sought to understand how a simple biological system, composed of a unique actin and a limited set of actin‐binding proteins, reacts to a switch to heterologous actin expression. Using yeast as a model system and biomimetic assays, we show that such perturbation causes drastic reorganization of the actin cytoskeleton. Our results indicate that defective interaction of a heterologous actin for important regulators of actin assembly limits certain actin assembly pathways while reinforcing others. Expression of two heterologous actin variants, each specialized in assembling a different network, rescues cytoskeletal organization and confers resistance to external perturbation. Hence, while species using a unique actin have homeostatic actin networks, actin assembly pathways in species using several actin isoforms may act more independently. SYNOPSIS: Why assembly of a complex actin cytoskeleton involves a single ortholog in some species and multiple isoforms in others is unclear. Here, actin gene swapping is used to understand how the yeast molecular machinery uses different actin variants, revealing a mechanism for functional segregation of similar actin isoforms into distinct networks. Reducing actin expression by half has negligible effects on budding yeast cell behavior.Minor modifications of the actin protein can disrupt interaction with an actin regulator, and funnel actin preferentially into assembly pathways not promoted by this regulator.Combination of two specialized actin variants that promote different actin organizations restores wild‐type actin configuration in yeast.Use of multiple specialized variants hampers efficient redistribution of actin between the different networks of the yeast cell. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index