Biology subjects

Xavier, A.

Publications and source records attributed to Xavier, A..

2 recordsLinked to original sources

bioRxiv2018

Panoptic vDISCO imaging reveals neuronal connectivity, remote trauma effects and meningeal vessels in intact transparent mice

Analysis of entire transparent rodent bodies could provide holistic information on biological systems in health and disease. However, it has been challenging to reliably image and quantify signal from endogenously expressed fluorescent proteins in large cleared mouse bodies due to the low signal contrast. Here, we devised a pressure driven, nanobody based whole-body immunolabeling technology to enhance the signal of fluorescent proteins by up to two orders of magnitude. This allowed us to image subcellular details in transparent mouse bodies through bones and highly autofluorescent tissues, and perform quantifications. We visualized for the first-time whole-body neuronal connectivity of an entire adult mouse and discovered that brain trauma induces degeneration of peripheral axons. We also imaged meningeal lymphatic vessels and immune cells through the intact skull and vertebra in naive animals and trauma models. Thus, our new approach can provide an unbiased holistic view of biological events affecting the nervous system and the rest of the body.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC=\"FIGDIR/small/374785_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (62K):\norg.highwire.dtl.DTLVardef@8fad72org.highwire.dtl.DTLVardef@c41ed5org.highwire.dtl.DTLVardef@1c470eaorg.highwire.dtl.DTLVardef@1d144cb_HPS_FORMAT_FIGEXP M_FIG C_FIG Note: Manuscript videos are available at Supplementary material section of BioRxiv and at the following link http://vdisco.isd-muc.de/

neuroscience↗

bioRxiv2018

Non-canonical role of E3 ligase RIPLET in innate immunity as a co-receptor for RIG-I

Ubiquitin (Ub) and its E3 ligases play diverse biological roles, from proteasomal degradation to innate immune signaling. The conventional view posits that E3 ligases function primarily through conjugating Ub to their substrate molecules. We report here that RIPLET, an essential E3 ligase in antiviral immunity, promotes the antiviral signaling activity of the viral RNA receptor RIG-I through both Ub-dependent and -independent manners. RIPLET utilizes its dimeric structure and the bivalent binding mode to preferentially recognize RIG-I preoligomerized on dsRNA. RIPLET can also adopt an alternative binding mode for filamentous oligomers of RIG-I assembled on longer dsRNAs, cross-bridging RIG-I filaments in both ubiquitin-dependent and-independent manners. The resultant receptor clustering leads to the formation of aggregate-like cytosolic granules and the stimulation of RIG-I-mediated antiviral signaling in a RNA-length dependent manner. These observations show the unexpected role of an E3 ligase as a co-receptor that directly participates in receptor oligomerization and ligand discrimination. This study also highlights previously unrecognized mechanisms by which an E3 ligase induces receptor clustering and signal amplification, and offers insights into the unique cellular function of membrane-less granule assembly.\n\nOne-sentence summaryRIPLET functions as a molecular glue to assemble signaling scaffolds for the antiviral innate immune receptor RIG-I.

immunology↗