Erk regulation of actin capping and bundling by Eps 8 promotes cortex tension and leader bleb - 1 based migration
نویسندگان
چکیده
15 Within the confines of tissues, cancer cells can use blebs to migrate. Eps8 is an actin bundling and 16 capping protein whose capping activity is inhibited by Erk, a key MAP kinase that is activated by 17 oncogenic signaling. We tested the hypothesis that Eps8 acts as an Erk effector to modulate actin 18 cortex mechanics and thereby mediate bleb-based migration of cancer cells. Cells confined in a non19 adhesive environment migrate in the direction of a very large “leader bleb.” Eps8 bundling activity 20 promotes cortex tension and intracellular pressure to drive leader bleb formation. Eps8 capping and 21 bundling activities act antagonistically to organize actin within leader blebs, and Erk mediates this effect. 22 An Erk biosensor reveals concentrated kinase activity within leader blebs. Bleb contents are trapped by 23 the narrow neck that separates the leader bleb from the cell body. Thus, Erk activity promotes actin 24 bundling by Eps8 to enhance cortex tension and drive the bleb-based migration of cancer cells under 25 non-adhesive confinement. 26
منابع مشابه
Erk regulation of actin capping and bundling by Eps8 promotes cortex tension and leader bleb-based migration
Within the confines of tissues, cancer cells can use blebs to migrate. Eps8 is an actin bundling and capping protein whose capping activity is inhibited by Erk, a key MAP kinase that is activated by oncogenic signaling. We tested the hypothesis that Eps8 acts as an Erk effector to modulate actin cortex mechanics and thereby mediate bleb-based migration of cancer cells. Cells confined in a non-a...
متن کاملRole of cortical tension in bleb growth.
Blebs are spherical membrane protrusions often observed during cell migration, cell spreading, cytokinesis, and apoptosis, both in cultured cells and in vivo. Bleb expansion is thought to be driven by the contractile actomyosin cortex, which generates hydrostatic pressure in the cytoplasm and can thus drive herniations of the plasma membrane. However, the role of cortical tension in bleb format...
متن کاملMolecular Basis for the Dual Function of Eps8 on Actin Dynamics: Bundling and Capping
Actin capping and cross-linking proteins regulate the dynamics and architectures of different cellular protrusions. Eps8 is the founding member of a unique family of capping proteins capable of side-binding and bundling actin filaments. However, the structural basis through which Eps8 exerts these functions remains elusive. Here, we combined biochemical, molecular, and genetic approaches with e...
متن کاملEzrin regulates microvillus morphogenesis by promoting distinct activities of Eps8 proteins
The mechanisms that regulate actin filament polymerization resulting in the morphogenesis of the brush border microvilli in epithelial cells remain unknown. Eps8, the prototype of a family of proteins capable of capping and bundling actin filaments, has been shown to bundle the microvillar actin filaments. We report that Eps8L1a, a member of the Eps8 family and a novel ezrin-interacting partner...
متن کاملEffect of Topiramate on Morphine-induced Conditioned Place Preference (CPP) in Rats: Role of ERK and CREB Proteins in Hippocampus and Cerebral Cortex
In this study, the effect of topiramate, as an antiepileptic drug, was evaluated on morphine craving in rats. The conditioned place preference (CPP) test was used for this purpose. Repeated administration of morphine (10 mg/kg, i.p. for 4 days) induced significant CPP. Administration of topiramate (50 and 100 mg/kg, i.p. for 4 days) with each morphine administration decreased the acquisition of...
متن کامل