Biology subjects

Inaba, M.

Publications and source records attributed to Inaba, M..

21 records · Page 2Linked to original sources

bioRxiv2020

Comparative analysis of antigen-specific anti-SARS-CoV-2 antibody isotypes in COVID-19 patients

Serological tests for detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in blood are expected to identify individuals who have acquired immunity against SARS-CoV-2 and indication of seroprevalence of SARS-CoV-2 infection. Many serological tests have been developed to detect antibodies against SARS-CoV-2. However, these tests have considerable variations in their specificity and sensitivity, and whether they can predict levels of neutralizing activity is yet to be determined. This study aimed to investigate the kinetics and neutralizing activity of various antigen-specific antibody isotypes against SARS-CoV-2 in serum of coronavirus disease 2019 (COVID-19) patients confirmed via polymerase chain reaction test. We developed IgG, IgM and IgA measurement assays for each antigen, including receptor-binding domain (RBD) of spike (S) protein, S1 domain, full length S protein, S trimer and nucleocapsid (N) domain, based on enzyme-linked immunosorbent assay. The assays of the S protein for all isotypes showed high specificity, while the assays for all isotypes against N protein showed lower specificity. The sensitivity of all antigen-specific antibody isotypes depended on the timing of the serum collection and all of them, except for IgM against N protein, reached more than 90% at 15-21 days post-symptom onset. The best correlation with virus neutralizing activity was found for IgG against RBD (RBD-IgG), and levels of RBD-IgG in sera from four severe COVID-19 patients increased concordantly with neutralizing activity. Our results provide valuable information regarding the selection of serological test for seroprevalence and vaccine evaluation studies.

immunology↗

bioRxiv2019

Mad dephosphorylation at the nuclear envelope is essential for asymmetric stem cell division

Stem cell niche signals act over a short range so that only stem cells but not the differentiating daughter cells receive the self-renewal signals. Drosophila female germline stem cells (GSCs) are maintained by short range BMP signaling; BMP ligands Dpp/Gbb activate receptor Tkv to phosphorylate Mad (phosphor-Mad or pMad) which accumulates in the GSC nucleus and activates the stem cell transcription program. pMad is highly concentrated in the nucleus of the GSC, but is immediately downregulated in the nucleus of the pre-cystoblast (preCB), a differentiating daughter cell, that is displaced away from the niche. Here we show that this asymmetry in the intensity of pMad is formed even before the completion of cytokinesis. A delay in establishing the pMad asymmetry leads to germline tumors through conversion of differentiating cells into a stem cell-like state. We show that a Mad phosphatase Dullard (Dd) interacts with Mad at the nuclear pore, where it may dephosphorylate Mad. A mathematical model explains how an asymmetry can be established in a common cytoplasm. It also demonstrates that the ratio of pMad concentrations in GSC/preCB is highly sensitive to Mad dephosphorylation rate. Our study reveals a previously unappreciated mechanism for breaking symmetry between daughter cells during asymmetric stem cell division.

developmental biology↗

bioRxiv2018

Stem cell receptor degradation by niche cells restricts signaling

Stem-cell niche signaling is short-range in nature, such that only stem cells but not their differentiating progeny experience self-renewing signals. At the apical tip of the Drosophila testes, 8 to 10 germline stem cells (GSCs) surround the hub, a cluster of somatic cells that function as the major component of the stem cell niche. We have shown that GSCs form microtubule-based nanotubes (MT-nanotubes), which project into the hub cells, serving as the platform for niche signal reception: the receptor Tkv expressed by GSCs localizes to the surface of MT-nanotubes, where it receives the hub-derived ligand Decapentaplegic (Dpp), ensuring the reception of the ligand specifically by stem cells but not by differentiating cells. Here we show that receptor (Tkv)-ligand (Dpp) interaction at the surface of MT-nanotubes serves a second purpose of dampening the niche signaling: we found that the receptor Tkv and the ligand Dpp are internalized into hub cells and are degraded in the hub cell lysosomes. Perturbation of hub lysosomal function or MT-nanotube formation leads to excess receptor retention within germ cells as well as excess Dpp that diffuses out of the hub, leading to ectopic activation of niche signal in differentiating germ cells. Our results demonstrate that MT-nanotubes plays dual roles in ensuring the short-range nature of the niche signaling by 1) providing exclusive interphase of the niche ligand-receptor interaction and 2) limiting the amount of available ligand-receptor via their degradation.

cell biology↗