Biology subjects

Toyama, Y.

Publications and source records attributed to Toyama, Y..

21 records · Page 2Linked to original sources

bioRxiv2019

Enhancement of endothelialization by topographical features is mediated by PTP1B-dependent endothelial adherens junctions remodeling

RationaleFailure of small synthetic vascular grafts is largely due to late endothelialization and has been an ongoing challenge in the treatment of cardiovascular diseases.\n\nObjectivePrevious strategies developed to promote graft endothelialization include surface topographical modulation and biochemical modifications. However, these have been met with limited success. Importantly, although the integrity of Endothelial Cell (EC) monolayer is crucial for endothelialization, the crosstalk between surface topography and cell-cell connectivity is still not well understood. Here we explored a combined strategy that utilizes both topographical features and pharmacological perturbations.\n\nMethods and resultWe characterized EC behaviors in response to micron-scale grating topography in conjunction with pharmacological perturbations of endothelial adherens junctions (EAJ) regulators. We studied the EA.hy 926 cell-cell junctions and monolayer integrity using the junctional markers upon the inhibitory effect of EAJ regulator on both planar and grating topographies substrates.\n\nWe identified a protein tyrosine phosphatase, PTP1B, as a potent regulator of EAJ stability. Next, we studied the physiologically relevant behaviors of EC using primary human coronary arterial endothelial cells (HCAEC). Our results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration to promote endothelialization.\n\nOur results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration and proliferation.\n\nConclusionThe synergistic effect of PTP1B inhibition and grating topographies could be useful for the promotion of endothelialization by enhancing EC migration and proliferation.

cell biology↗

bioRxiv2019

Mechanical Roles of Vinculin/β-catenin interaction in Adherens Junction

Mechanical force transmission through the adherens junctions (AJs) are highly regulated processes essential for multicellular organization of tissues. AJ proteins such as E-cadherin, -catenin, and vinculin have been shown to be sensing or bearing mechanical forces being transmitted between the actin cytoskeleton and the intercellular contacts. However, the molecular organization and connectivity of these components remains not well understood. Using a super-resolution microscopy approach, we report that vinculin, once activated, could form a direct structural connection with {beta}-catenin, which can bypass -catenin, one of the main mechanotransducers in AJs. Direct vinculin/{beta}-catenin interaction is capable of supporting mechanical tension and contributes to the stabilization of the cadherin-catenin complexes. These findings suggest a multi-step model for the force-dependent reinforcement of AJs whereby -catenin may serve as the initial catalytic activator of vinculin, followed by vinculin translocation to form a direct link between E-cadherin-bound {beta}-catenin and the actin cytoskeleton.

cell biology↗

bioRxiv2017

Neurexin and Neuroligin-based adhesion complexes drive axonal arborisation growth independent of synaptic activity

Building arborisations of the right size and shape is fundamental for neural network function. Live imaging studies in vertebrate brains strongly suggest that nascent synapses are critical for branch growth during the development of axonal and dendritic arborisations. The molecular mechanisms underlying such synaptotropic events are largely unknown.\n\nHere we present a novel system in Drosophila for studying the development of complex axonal arborisations live, in vivo during metamorphosis. In these growing axonal arborisations we see a relationship between the punctate localisations of presynaptic components and branch dynamics that is very similar to synaptotropic growth described in fish and frogs. These presynaptic components however do not appear to represent functional presynaptic release sites and are not paired with clusters of neurotransmitter receptors. Pharmacological and genetic knockdowns of evoked and spontaneous neurotransmission do not impact the outgrowth of these neurons. Instead, we find that axonal branch growth is regulated by the dynamic focal localisations of synaptic adhesion proteins Neurexin and Neuroligin. These adhesion complexes provide selective stability for filopodia by a stick and grow-based mechanism wholly independent of synaptic activity.

neuroscience↗