Biology subjects

Erofeev, I. S.

Publications and source records attributed to Erofeev, I. S..

3 recordsLinked to original sources

bioRxiv2021

Mechanosensitive calcium signaling promotes epithelial tight junction remodeling by activating RhoA

Epithelia maintain an effective barrier by actively remodeling cell-cell junctions in response to mechanical stimuli. Cells often respond to mechanical stress through activation of RhoA and dynamic remodeling of actomyosin. Previously, we found that local leaks in the epithelial tight junction barrier are rapidly repaired by localized, transient activation of RhoA, a process we termed "Rho flares", but how Rho flares are initiated remains unknown. Here, we discovered that intracellular calcium flashes occur in Xenopus laevis embryonic epithelial cells undergoing rapid remodeling of tight junctions via activation of Rho flares. Calcium flashes originate at the site of leaks and propagate into the cell. Depletion of intracellular calcium or inhibition of mechanosensitive calcium channels (MSC) reduced the amplitude of calcium flashes and diminished the activation of Rho flares. Furthermore, MSC-dependent calcium influx was necessary to maintain global barrier function by regulating repair of local tight junction proteins through efficient contraction of junctions. Collectively, we propose that MSC-dependent calcium flashes are an important mechanism allowing epithelial cells to sense and respond to local leaks induced by mechanical stimuli.

cell biology↗

bioRxiv2020

Cortical myosin minifilaments orchestrate the arrangement of microridge protrusions on epithelial cell surfaces

Actin-based protrusions vary in morphology, stability, and arrangement on cell surfaces. Microridges are laterally-elongated protrusions arranged in maze-like patterns on mucosal epithelial cells that rearrange dynamically by fission and fusion. To characterize how microridges mature and investigate the mechanisms driving fission and fusion, we imaged microridges in the maturing skin of zebrafish larvae. After their initial development, microridges continued to lengthen and microridge alignment became increasingly well ordered. Imaging F-actin and Non-Muscle Myosin II (NMII) revealed that microridge fission and fusion were associated with local NMII activity in the apical cortex. Inhibiting NMII blocked rearrangements, reduced microridge density, and altered microridge spacing. High-resolution imaging revealed that individual cortical NMII minifilaments are tethered to protrusions, often connecting adjacent microridges. NMII minifilaments connecting the ends of microridges fused them together, whereas minifilaments oriented perpendicular to microridges severed them or pulled them closer together. Our findings demonstrate that as cells mature, microridges continue to remodel and form an increasingly orderly arrangement through a process orchestrated by cortical NMII contraction.

cell biology↗

bioRxiv2019

Cortical contraction drives the 3D patterning of epithelial cell surfaces

Cellular protrusions create complex cell surface topographies, but biomechanical mechanisms regulating their formation and arrangement are largely unknown. To study how protrusions form, we focused on the morphogenesis of microridges, elongated actin-based structures projecting from the apical surfaces of zebrafish skin cells that are arranged in labyrinthine patterns. Microridges form by accreting simple finger-like precursors. Live imaging demonstrated that microridge morphogenesis is linked to apical constriction. A non-muscle myosin II (NMII) reporter revealed pulsatile contractions of the actomyosin cortex; inhibiting NMII demonstrated that contractions are required for apical constriction and microridge formation. A biomechanical model suggested that contraction reduces surface tension to permit the fusion of precursors into microridges. Indeed, reducing surface tension with hyperosmolar media promoted microridge formation. In anisotropically stretched cells, microridges formed by precursor fusion along the stretch axis, which computational modeling explained as a consequence of stretch-induced cortical flow. Collectively, our results demonstrate how contraction within the 2D plane of the cortex patterns 3D cell surfaces.\n\nSUMMARYMicroridges, elongated 3D protrusions arranged in maze-like patterns on zebrafish skin cells, form by the accretion of simple precursor projections. Modeling and in vivo experiments showed that cortical contractions promote the coalescence of precursors into microridges by reducing membrane tension.

cell biology↗