Language：Japanese  

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Language：English   Publishing type：Research paper (scientific journal)  

Actin-mediated mechanical forces are central drivers of cellular dynamics. They generate protrusive and contractile dynamics, the latter of which are induced in concert with myosin II bundled at the site of contraction. These dynamics emerge concomitantly in tissues and even each cell; thus, the tight regulation of such bidirectional forces is important for proper cellular deformation. Here, we show that contractile dynamics can eventually disturb cell-cell junction contraction in the absence of p21-activated kinase 3 (Pak3). Upon Pak3 depletion, contractility induces the formation of abnormal actin protrusions at the shortening junctions, which causes decrease in E-cadherin levels at the adherens junctions and mislocalization of myosin II at the junctions before they enough shorten, compromising completion of junction shortening. Overexpressing E-cadherin restores myosin II distribution closely placed at the junctions and junction contraction. Our results suggest that contractility both induces and perturbs junction contraction and that the attenuation of such perturbations by Pak3 facilitates persistent junction shortening.

DOI： 10.1038/s41467-022-31252-0

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Nanometer-level patterned surface structures form the basis of biological functions, including superhydrophobicity, structural coloration, and light absorption [1-3]. In insects, the cuticle overlying the olfactory sensilla has multiple small (50- to 200-nm diameter) pores [4-8], which are supposed to function as a filter that admits odorant molecules, while preventing the entry of larger airborne particles and limiting water loss. However, the cellular processes underlying the patterning of extracellular matrices into functional nano-structures remain unknown. Here, we show that cuticular nanopores in Drosophila olfactory sensilla originate from a curved ultrathin film that is formed in the outermost envelope layer of the cuticle and secreted from specialized protrusions in the plasma membrane of the hair forming (trichogen) cell. The envelope curvature coincides with plasma membrane undulations associated with endocytic structures. The gore-tex/Osiris23 gene encodes an endosomal protein that is essential for envelope curvature, nanopore formation, and odor receptivity and is expressed specifically in developing olfactory trichogen cells. The 24-member Osiris gene family is expressed in cuticle-secreting cells and is found only in insect genomes. These results reveal an essential requirement for nanopores for odor reception and identify Osiris genes as a platform for investigating the evolution of surface nano-fabrication in insects.

DOI： 10.1016/j.cub.2019.03.043

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41467-017-00494-8

Web of Science

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Language：English   Publishing type：Research paper (scientific journal)  

Proper function of the neural network results from the precise connections between axons and dendrites of presynaptic and postsynaptic neurons, respectively. In the Drosophila olfactory system, the dendrites of projection neurons (PNs) stereotypically target one of ∼50 glomeruli in the antennal lobe (AL), the primary olfactory center in the brain, and form synapses with the axons of olfactory receptor neurons (ORNs). Here, we show that Eph and Ephrin, the well-known axon guidance molecules, instruct the dendrodendritic segregation during the discrete olfactory map formation. The Eph receptor tyrosine kinase is highly expressed and localized in the glomeruli related to reproductive behavior in the developing AL. In one of the pheromone-sensing glomeruli (DA1), the Eph cell-autonomously regulates its dendrites to reside in a single glomerulus by interacting with Ephrins expressed in adjacent PN dendrites. Our data demonstrate that the trans interaction between dendritic Eph and Ephrin is essential for the PN dendritic boundary formation in the DA1 olfactory circuit, potentially enabling strict segregation of odor detection between pheromones and the other odors.

DOI： 10.1101/gad.297424.117

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acschembio.6b00586

Web of Science

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1073/pnas.1606731113

Web of Science

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/ncomms11046

Web of Science

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Authorship：Lead author   Language：English  

Neural circuit assembly requires precise dendrite and axon targeting. We identified an evolutionarily conserved endoplasmic reticulum (ER) protein, Meigo, from a mosaic genetic screen in Drosophila melanogaster. Meigo was cell-autonomously required in olfactory receptor neurons and projection neurons to target their axons and dendrites to the lateral antennal lobe and to refine projection neuron dendrites into individual glomeruli. Loss of Meigo induced an unfolded protein response and reduced the amount of neuronal cell surface proteins, including Ephrin. Ephrin overexpression specifically suppressed the projection neuron dendrite refinement defect present in meigo mutant flies, and ephrin knockdown caused a similar projection neuron dendrite refinement defect. Meigo positively regulated the level of Ephrin N-glycosylation, which was required for its optimal function in vivo. Thus, Meigo, an ER-resident protein, governs neuronal targeting specificity by regulating ER folding capacity and protein N-glycosylation. Furthermore, Ephrin appears to be an important substrate that mediates Meigo's function in refinement of glomerular targeting.

DOI： 10.1038/nn.3389

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Authorship：Lead author   Language：English  

Eukaryotic cells contain multiple intracellular organelles which are structurally and functionally distinct membrane-delimited compartments. Organelles play vital roles in many cellular events in essentially all eukaryotic cells. Although the canonical roles of organelles are well described by classical in vitro studies, little is known about the specific physiological roles of organelles in neurons, which possess extremely polarized cellular structures and have a massive cellular volume compared with most eukaryotic cells. Studies that make use of recently developed genetic and microscopic techniques are currently elucidating the unexpectedly specialized roles of intracellular, membrane-delimited organelles in neuronal morphogenesis and function, and in human disease. Here we review recent advances in understanding the roles of organelles (the ER-Golgi secretory pathway, endosomes and mitochondria) in developing neurons.

DOI： 10.1387/ijdb.082618ss

PubMed

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Language：English   Presentation type：Symposium, workshop panel (nominated)  

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Language：English   Presentation type：Oral presentation (invited, special)  

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Language：English   Presentation type：Symposium, workshop panel (nominated)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Language：English   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Language：English   Presentation type：Oral presentation (general)  

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