RT Journal Article
SR Electronic
T1 The conserved Pelado/ZSWIM8 protein regulates actin dynamics by promoting linear actin filament polymerization
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201484
DO 10.26508/lsa.202201484
VO 5
IS 12
A1 Claudia Molina-Pelayo
A1 Patricio Olguin
A1 Marek Mlodzik
A1 Alvaro Glavic
YR 2022
UL https://www.life-science-alliance.org/content/5/12/e202201484.abstract
AB Actin filament polymerization can be branched or linear, which depends on the associated regulatory proteins. Competition for actin monomers occurs between proteins that induce branched or linear actin polymerization. Cell specialization requires the regulation of actin filaments to allow the formation of cell type–specific structures, like cuticular hairs in Drosophila, formed by linear actin filaments. Here, we report the functional analysis of CG34401/pelado, a gene encoding a SWIM domain–containing protein, conserved throughout the animal kingdom, called ZSWIM8 in mammals. Mutant pelado epithelial cells display actin hair elongation defects. This phenotype is reversed by increasing actin monomer levels or by either pushing linear actin polymerization or reducing branched actin polymerization. Similarly, in hemocytes, Pelado is essential to induce filopodia, a linear actin-based structure. We further show that this function of Pelado/ZSWIM8 is conserved in human cells, where Pelado inhibits branched actin polymerization in a cell migration context. In summary, our data indicate that the function of Pelado/ZSWIM8 in regulating actin cytoskeletal dynamics is conserved, favoring linear actin polymerization at the expense of branched filaments.