ERK builds a population of short-lived nascent adhesions that produce persistent edge protrusion and cell migration

• 成果类型: Article
• 署名作者: Shepherd, Andrew P.; Carney, Keith R.; Rostami, Majid; Shawon, Jakaria; Elliott, Andrew; Samson, Shiela C.; Han, Sangyoon J.; Mendoza, Michelle C.
• 署名单位: Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah; Huntsman Cancer Institute; Michigan Technological University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2525452123
• 发表日期: 2026-06-23
• 页码: e2525452123
• 关键词: cell migration; erk; nascent adhesion; persistence; protrusion; actin; activation; kinase; fak; phosphorylation; DYNAMICS; paxillin; scaffold; GIT1; LAMELLIPODIUM

摘要

Cell migration is realized through the fast and persistent protrusion of a leading edge in the direction of movement. The actin and adhesion structures that build edge protrusions are integrated such that pro-migration signaling pathways must control both assemblies to induce protrusion. Understanding the contribution of adhesion regulation has been complicated by the inability to selectively assay the nascent adhesions that promote edge protrusion. Here, we dissect how the core RAS -> RAF -> MEK -> ERK pathway's control of nascent adhesions contributes to edge protrusion and cell migration by targeting an ERK FRET biosensor to adhesions and quantifying ERK's spatial and temporal activity. We find that ERK is activated in the assembling, membrane-proximal region of nascent adhesions through adhesion scaffold paxillin, which interacts with the ERK activator MEK. Tracking nascent adhesion dynamics during cell migration showed that ERK promotes both nascent adhesion assembly and disassembly to create a population of nascent adhesions with short lifetimes. MEK inhibition is partially complemented by expression of a talin R8vvv mutant that increases the nascent adhesion population, demonstrating the significance of ERK's adhesion regulation for edge protrusion and migration persistence. These findings suggest that when new adhesions initiate, the ERK activation level dictates adhesion assembly and disassembly rates to specifically build nascent adhesions that rapidly turn over, an adhesion population that promotes protrusion persistence and migration.