Self-construction of actin networks through phase separation–induced abLIM1 condensates

• DOI: 10.1073/pnas.2122420119
• Publication Date: 2022-07-11T19:16:06Z
• Authors: Sen Yang; Chunxia Liu; Yuting Guo; Guoqing Li; Dong Li; Xiumin Yan; Xueliang Zhu
• Keywords: 0301 basic medicine; Actin Cytoskeleton; 03 medical and health sciences; Microfilament Proteins; Humans; Protein Isoforms; RNA Interference; Biological Sciences; LIM Domain Proteins; Actins

The abLIM1 is a nonerythroid actin-binding protein critical for stable plasma membrane–cortex interactions under mechanical tension. Its depletion by RNA interference results in sparse, poorly interconnected cortical actin networks and severe blebbing of migrating cells. Its isoforms, abLIM-L, abLIM-M, and abLIM-S, contain, respectively four, three, and no LIM domains, followed by a C terminus entirely homologous to erythroid cortex protein dematin. How abLIM1 functions, however, remains unclear. Here we show that abLIM1 is a liquid–liquid phase separation (LLPS)-dependent self-organizer of actin networks. Phase-separated condensates of abLIM-S-mimicking ΔLIM or the major isoform abLIM-M nucleated, flew along, and cross-linked together actin filaments (F-actin) to produce unique aster-like radial arrays and interconnected webs of F-actin bundles. Interestingly, ΔLIM condensates facilitated actin nucleation and network formation even in the absence of Mg2+. Our results suggest that abLIM1 functions as an LLPS-dependent actin nucleator and cross-linker and provide insights into how LLPS-induced condensates could self-construct intracellular architectures of high connectivity and plasticity.