Dataset Information

AbLIM1 constructs non-erythroid cortical actin networks to prevent mechanical tension-induced blebbing.

ABSTRACT: The cell cortex is a layer of cytoskeletal networks underneath the plasma membrane, formed by filamentous actin (F-actin) and cortex proteins including spectrin, adducin, and myosin. It provides cells with proper stiffness, elasticity, and surface tension to allow morphogenesis, division, and migration. Although its architecture and formation have been widely studied in red blood cells, they are poorly understood in non-erythrocytes due to structural complexity and versatile functions. In this study, we identify the actin-binding protein abLIM1 as a novel non-erythroid cell-specific cortex organizer. Endogenous abLIM1 colocalized with cortical ?II spectrin but upon overexpression redistributed to thick cortical actin bundles. abLIM1 associated with major cortex proteins such as spectrins and adducin in vivo. Depletion of abLIM1 by RNAi induced prominent blebbing during membrane protrusions of spreading or migrating RPE1 cells and impaired migration efficiency. Reducing cortical tensions by culturing the cells to confluency or inhibiting myosin activity repressed the blebbing phenotype. abLIM1-depleted RPE1 or U2OS cells lacked the dense interwoven cortical actin meshwork observed in control cells but were abundant in long cortical actin bundles along the long axis of the cells. In-vitro assays indicated that abLIM1 was able to crosslink and bundle F-actin to induce dense F-actin network formation. Therefore, abLIM1 governs the formation of dense interconnected cortical actin meshwork in non-erythroid cells to prevent mechanical tension-induced blebbing during cellular activities such as spreading and migration.

SUBMITTER: Li G

PROVIDER: S-EPMC6056535 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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abLIM1 constructs non-erythroid cortical actin networks to prevent mechanical tension-induced blebbing.

Li Guoqing G Huang Shan S Yang Sen S Wang Jiabin J Cao Jingli J Czajkowsky Daniel M DM Shao Zhifeng Z Zhu Xueliang X

Cell discovery 20180724

The cell cortex is a layer of cytoskeletal networks underneath the plasma membrane, formed by filamentous actin (F-actin) and cortex proteins including spectrin, adducin, and myosin. It provides cells with proper stiffness, elasticity, and surface tension to allow morphogenesis, division, and migration. Although its architecture and formation have been widely studied in red blood cells, they are poorly understood in non-erythrocytes due to structural complexity and versatile functions. In this s ...[more]

PMID: 30062045

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Project description:Mechanical stability is a fundamental and essential property of epithelial cell sheets. It is in large part determined by cell-cell adhesion sites that are tightly integrated by the cortical cytoskeleton. An intimate crosstalk between the adherens junction-associated contractile actomyosin system and the desmosome-anchored keratin intermediate filament system is decisive for dynamic regulation of epithelial mechanics. A major question in the field is whether and in which way mechanical stress affects junctional plasticity. This is especially true for the desmosome-keratin scaffold whose role in force-sensing is virtually unknown. To examine this question, we inactivated the actomyosin system in human keratinocytes (HaCaT) and canine kidney cells (MDCK) and monitored changes in desmosomal protein turnover. Partial inhibition of myosin II by para-nitro-blebbistatin led to a decrease of the cells' elastic modulus and to reduced desmosomal protein turnover in regions where nascent desmosomes are formed and, to a lower degree, in regions where larger, more mature desmosomes are present. Interestingly, desmosomal proteins are affected differently: a significant decrease in turnover was observed for the desmosomal plaque protein desmoplakin I (DspI), which links keratin filaments to the desmosomal core, and the transmembrane cadherin desmoglein 2 (Dsg2). On the other hand, the turnover of another type of desmosomal cadherin, desmocollin 2 (Dsc2), was not significantly altered under the tested conditions. Similarly, the turnover of the adherens junction-associated E-cadherin was not affected by the low doses of para-nitro-blebbistatin. Inhibition of actin polymerization by low dose latrunculin B treatment and of ROCK-driven actomyosin contractility by Y-27632 treatment also induced a significant decrease in desmosomal DspI turnover. Taken together, we conclude that changes in the cortical force balance affect desmosome formation and growth. Furthermore, they differentially modulate desmosomal protein turnover resulting in changes of desmosome composition. We take the observations as evidence for a hitherto unknown desmosomal mechanosensing and mechanoresponse pathway responding to an altered force balance.

Dataset Information

AbLIM1 constructs non-erythroid cortical actin networks to prevent mechanical tension-induced blebbing.

Publications

abLIM1 constructs non-erythroid cortical actin networks to prevent mechanical tension-induced blebbing.

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