Biology subjects

Yamashiro, Y.

Publications and source records attributed to Yamashiro, Y..

4 recordsLinked to original sources

bioRxiv2023

Zinc finger domains bind low-complexity domain polymers

Self-association of low-complexity protein sequences (LC domains) is important for polymer formation. Several molecular chaperones are involved in the regulation of LC domain polymer formation. However, the mechanisms underlying cell recognition of LC domain polymers remain unclear. Here we show that zinc finger domains (ZnFs) bind LC domains of RNA-binding proteins in a cross-{beta} polymer-dependent manner. ZnFs bound to LC domain hydrogels and suppressed LC domain polymer formation. Moreover, ZnFs preferentially recognize LC domains in the polymeric state. These findings suggest that ZnFs act as physiological regulators of LC domain polymer formation.

biochemistry↗

bioRxiv2021

Partial endothelial-to-mesenchymal transition (EndMT) contributes to lumen re-organization after carotid arteryligation

Endothelial-to-mesenchymal transition (EndMT) is a fundamental process in vascular remodeling. Carotid artery ligation is commonly used for induction of neointima formation and vessel stenosis; however, the precise regulatory mechanism of vascular remodeling is not entirely understood. In this study, we showed that resident endothelial cells (ECs) are the origin of neointima cells and ECs transiently expressed CD45 in the early stage of neointima formation accompanied by increased expression of EndMT markers. In vitro, CD45-positive EndMT was induced by stabilization of HIF-1 with cobalt chloride or VHL inhibitor in human primary ECs, which mimicked the hypoxic condition of ligated artery, and promoted the formation of integrin 11-SHARPIN complex. Notably, a CD45 phosphatase inhibitor disrupted this complex, thereby destabilizing cell-cell junctions. These results suggest that the CD45 activity is required for the retention of an EC phenotype and cell-cell junctions during EndMT (termed "partial EndMT"). We thus propose a novel mechanism of partial EndMT that contributes to lumen re-organization during vascular injury.

molecular biology↗

bioRxiv2020

C9orf72- derived proline:arginine poly-dipeptides disturb cytoskeletal architecture

Amyotrophic lateral sclerosis (ALS) is an irreversible neurodegenerative disease caused by the degeneration of motor neurons, and cytoskeletal instability is considered to be involved in neurodegeneration. A hexanucleotide repeat expansion of the C9orf72, one of the most common causes of familial ALS, produces toxic proline:arginine (PR) poly-dipeptides. PR poly-dipeptides binds polymeric forms of low complexity sequences and intracellular puncta, thereby altering intermediate filaments (IFs). However, how PR poly-dipeptides affect the cytoskeleton, including IFs, microtubules and actin filaments, remains unknown. Here we performed a synthetic PR poly-dipeptide treatment on mammalian cells and investigated how it affects morphology of cytoskeleton and cell behaviors. We observed that PR poly-dipeptide treatment induce the degradation of vimentin bundles at perinucleus and dissociation of {beta}-tubulin network. PR poly-dipeptides also lead to alteration of actin filaments toward to cell contours and strength cortical actin filaments via activation of ERM (ezrin/radixin/moesin) proteins. In addition, we found that PR poly-dipeptides promote phosphorylation of paxillin and recruitment of vinculin on focal adhesions, which lead to maturation of focal adhesions. Finally, we evaluated the effects of PR poly-dipeptides on mechanical property and stress response. Interestingly, treatment of PR poly-dipeptides increased the elasticity of the cell surface, leading to maladaptive response to cyclic stretch. These results suggest that PR poly-dipeptides cause mechanically sensitive structural reorganization and disrupt the cytoskeleton architecture.

biochemistry↗

bioRxiv2019

Matrix mechanotransduction mediated by thrombospondin-1/integrin/YAP signaling pathway in the remodeling of blood vessels

RationaleThe extracellular matrix (ECM) initiates mechanical cues and transduces intracellular signaling through matrix-cell interactions. In the blood vessels, additional mechanical cues derived from the pulsatile blood flow and pressure play a pivotal role in homeostasis and disease development. Currently, the nature of the cues from ECM and how they coordinate with a mechanical microenvironment in large blood vessels to maintain the integrity of the vessel wall are not fully understood.\n\nObjectiveThe aim of this study was to elucidate the crucial mediator(s) and molecular signaling pathway(s) involved in matrix mechanotransduction during remodeling of the vessel wall.\n\nMethods and ResultsWe performed secretome analysis using rat vascular smooth muscle cells (SMCs) under cyclic stretch and examined matrix-cell interactions and cell behavior. We found that the matricellular protein thrombospondin-1 (Thbs1) was secreted upon cyclic stretch and bound to integrin v{beta}1, thereby recruiting vinculin and establishing focal adhesions. RNA-sequence (RNA-seq) analysis revealed that deletion of Thbs1 in vitro markedly affected the target gene expression of Yes-associated protein (YAP). Consistently, we found that Thbs1 promotes nuclear shuttling of YAP in response to cyclic stretch, which depends on the small GTPase Rap2 and Hippo pathway, and is not influenced by alteration of actin fibers. Deletion of Thbs1 in mice inhibited Thbs1/integrin/YAP signaling, leading to maladaptive remodeling of the aorta in response to pressure overload by transverse aortic constriction (TAC), whereas it suppressed neointima formation upon carotid artery ligation, exerting context-dependent effects on the vessel wall.\n\nConclusionsThbs1 serves as a mechanical stress-triggered extracellular mediator of mechanotransduction that acts via integrin v{beta}1 to establish focal adhesions and promotes nuclear shuttling of YAP. We thus propose a novel mechanism of matrix mechanotransduction centered on Thbs1, connecting mechanical stimuli to YAP signaling during vascular remodeling in vivo.\n\nSubject codesO_LIVascular Disease\nC_LIO_LIGenetically Altered and Transgenic Models\nC_LIO_LIVascular Biology\nC_LIO_LICell Signaling/Signal Transduction\nC_LI

molecular biology↗