Faculty, Staff and Student Publications
N-terminal α-Amino SUMOylation of Cofilin-1 Is Critical for Its Regulation of Actin Depolymerization
Publication Date
9-14-2023
Journal
Nature Communications
Abstract
Small ubiquitin-like modifier (SUMO) typically conjugates to target proteins through isopeptide linkage to the ε-amino group of lysine residues. This posttranslational modification (PTM) plays pivotal roles in modulating protein function. Cofilins are key regulators of actin cytoskeleton dynamics and are well-known to undergo several different PTMs. Here, we show that cofilin-1 is conjugated by SUMO1 both in vitro and in vivo. Using mass spectrometry and biochemical and genetic approaches, we identify the N-terminal α-amino group as the SUMO-conjugation site of cofilin-1. Common to conventional SUMOylation is that the N-α-SUMOylation of cofilin-1 is also mediated by SUMO activating (E1), conjugating (E2), and ligating (E3) enzymes and reversed by the SUMO deconjugating enzyme, SENP1. Specific to the N-α-SUMOylation is the physical association of the E1 enzyme to the substrate, cofilin-1. Using F-actin co-sedimentation and actin depolymerization assays in vitro and fluorescence staining of actin filaments in cells, we show that the N-α-SUMOylation promotes cofilin-1 binding to F-actin and cofilin-induced actin depolymerization. This covalent conjugation by SUMO at the N-α amino group of cofilin-1, rather than at an internal lysine(s), serves as an essential PTM to tune cofilin-1 function during regulation of actin dynamics.
Keywords
Actins, Sumoylation, Lysine, Actin Depolymerizing Factors, Ubiquitin, Sumoylation, Actin, Sumoylated proteins
DOI
10.1038/s41467-023-41520-2
PMID
37709794
PMCID
PMC10502023
PubMedCentral® Posted Date
9-14-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes