Biology subjects

Matsusaki, M.

Publications and source records attributed to Matsusaki, M..

3 recordsLinked to original sources

bioRxiv2021

Oxidative phase transition of heat shock factor-1

Heat shock factor 1 (Hsf1) was found as a central upregulator of molecular chaperones in stress adaptation, but it has recently been rediscovered as a major component of persistent nuclear stress bodies (nSBs). When the persistently stressed cells undergo apoptosis, the phase transition of nSBs from fluid to gel-like states is proposed to be an important event in switching the cell fate from survival to death. Nonetheless, how the phase separation and transition of nSBs are driven remain unanswered. In this study, we discovered that Hsf1 formed liquid-liquid phase separation droplets in vitro, causing the assembly of Hsf1 to drive nSBs formation. Under oxidative conditions, disulfide-bonded and oligomerized Hsf1 formed gel-like and more condensed droplets, confirmed through fluorescence recovery, refractive index imaging, and light scattering. Then, on the basis of our results, we proposed that Hsf1 undergoes oxidative phase transition by sensing redox conditions potentially to drive the cell fate decision by nSBs.

biochemistry↗

bioRxiv2020

Injectable prevascularized mature adipose tissues (iPAT) to achieve long-term survival in soft tissues regeneration

Soft tissue regeneration remains a challenge in reconstructive surgery. Current autologous fat implantations lead to high fat absorption ratios, while artificial implants can be associated with lymphoma occurrence. To overcome these limitations, our aim was to reproduce adipose tissue vasculature structure before implantation. Here, we developed injectable prevascularized adipose tissues (iPAT), using physiological collagen microfibers (CMF) mixed with human mature adipocytes, adipose-derived stem cells (ADSC) and human umbilical vein endothelial cells (HUVEC). Following murine subcutaneous implantation, higher cell survival (84{+/-}6% viability) and volume maintenance were shown after 3 months for the iPAT (up to twice heavier than the non-prevascularized balls). This higher survival can be explained by the greater amount of blood vessels (up to 1.6 folds increase), with balanced host anastomosis (51{+/-}1% of human/mouse lumens), also involving infiltration by the lymphatic and neural vasculature networks. These iPAT tissues allowed non-invasive soft tissue reconstruction for long-term outcomes, and the ability to cryopreserve them with maintained viability and functionality also enables a later reinjection usually required before reaching the final patient desired graft volume.

bioengineering↗

bioRxiv2020

A unique adhesive motif of protein disulfide isomerase P5 supports its function via dimerization

P5, also known as PDIA6, is a PDI-family member that plays an important role in the ER quality control. Herein, we revealed that P5 dimerizes via a unique adhesive motif contained in the N-terminal thioredoxin-like domain. This motif is apparently similar to, but radically different from conventional leucine-zipper motifs, in that the former includes a periodic repeat of leucine or valine residues at the third or fourth position spanning five helical turns on 15-residue anti-parallel -helices, unlike the latter of which the leucine residues appear every two helical turns on [~]30-residue parallel -helices at dimer interfaces. A monomeric P5 mutant with the impaired adhesive motif showed structural instability and local unfolding, and behaved as an aberrant protein that induces the ER stress response. Disassembly of P5 to monomers compromised its ability to inactivate IRE1 via reduction of intermolecular disulfide bonds and its Ca2+-dependent regulation of chaperone function in vitro. Thus, the leucine-valine adhesive motif supports structure and physiological function of P5.

biochemistry↗