Biology subjects

Kanno, M.

Publications and source records attributed to Kanno, M..

3 recordsLinked to original sources

bioRxiv2025

An Innate Immune Receptor Toll-1 converts chronic light stress into glial phagocytosis

Chronic stress can cause progressive neuronal degeneration, yet the molecular mechanisms linking stress sensing to neuroimmune responses remain elusive. In this study, using a Drosophila model of chronic light-induced stress, we show that photoreceptor neurons accumulate reactive oxygen species (ROS) and exhibit Toll-1 activation which involves Spatzle ligands and receptor endocytosis. Toll-1 activation in neurons promotes axonal degeneration by inducing expression of the glial phagocytic receptor Draper (Drpr), leading to the engulfment of stressed axons. Genetic interaction analyses indicate that Toll-1 functions upstream of Drpr in a stress-responsive signaling cascade. Blocking either Toll-1 or Drpr attenuates axon loss under light stress, while Toll-1 overexpression exacerbates it. Toll-1 also plays a similar pro-degenerative role in an activity-dependent olfactory neuron degeneration paradigm, pointing to a broader role for this mechanism in neural degeneration. Together, these findings identify a neuron-glia signaling axis that converts sustained stress into structural degeneration.

neuroscience↗

bioRxiv2024

Extracellular vesicles adhere to cells predominantly through the interaction of CD151-associated integrin heterodimers and GM1 with laminin

Tumor-derived extracellular vesicles (EVs) have attracted significant attention, yet the molecular mechanisms that govern their specific binding to recipient cells remain elusive. Our in vitro study utilizing single-particle tracking demonstrated that integrin heterodimers comprising 6{beta}4 and 6{beta}1 and ganglioside, GM1 are responsible for the binding of small-EV (sEV) subtypes to laminin. EVs derived from four distinct tumor cell lines, regardless of size, exhibited high binding affinities for laminin but not for fibronectin, although fibronectin receptors are abundant in EVs and have functional roles in EV-secreting cells. Our findings revealed that integrins in EVs bind to laminin via the conventional molecular interface, facilitated by CD151 rather than by inside-out signaling of talin-1 and kindlin-2. Super-resolution movie observation revealed that sEV integrins bind only to laminin on living recipient cells. Furthermore, sEVs bound to HUVEC and induced cell branching morphogenesis in a laminin-dependent manner. Thus, we demonstrated that EVs predominantly bind to laminin on recipient cells, which is indispensable for cell responses. SummaryQuantitative assessments using single-molecule imaging and super-resolution microscopy revealed that all extracellular vesicle subtypes derived from four distinct tumor cell lines, regardless of size, bind to laminin predominantly via CD151-facilitated integrin heterodimers and GM1, leading to response of recipient cells.

cell biology↗

bioRxiv2023

Translational regulation enhances distinction of cell types in the nervous system

Multicellular organisms are composed of specialized cell types with distinct proteomes. While recent advances in single-cell transcriptome analyses have revealed differential expression of mRNAs, cellular diversity in translational profiles remains underinvestigated. By performing RNA-seq and Ribo-seq in genetically-defined cells in the Drosophila brain, we here revealed substantial posttranscriptional regulations that augment the cell-type distinctions at the level of protein expression. Specifically, we found that translational efficiency of proteins fundamental to neuronal functions, such as ion channels and neurotransmitter receptors, was maintained low in glia, leading to their preferential translation in neurons. Notably, distribution of ribosome footprints on these mRNAs exhibited a remarkable bias towards the 5' leaders in glia. Using transgenic reporter strains, we provide evidence that the small upstream open reading frames (uORFs) in the 5 leader confer selective translational suppression in glia. Overall, these findings underscore the profound impact of translational regulation in shaping the proteomics for cell-type distinction and provide new insights into the molecular mechanisms driving cell-type diversity.

neuroscience↗