Division of Cell Structure
Member
Molecular basis of cell-cell junctions involved in epithelial barrier function
The Epithelium separates body compartments as a barrier and selectively transports various substances, thereby contributing to various functions of organs and homeostasis. Our laboratory aims to clarify the molecular bases of specialized cell structures that are responsible for these basic roles of the epithelium. We focus on the cell-cell junctions involved in the regulation of paracellular transport (occluding junctions), including the tight junction and its related structures, and examine their molecular architectures, functions and dynamic behavior. One of the characteristic features of our research is that we identify structural or regulatory proteins of occluding junctions in our hands and characterize them. We take combined approaches of molecular biology, physiology and morphology, including immunoelectron and freeze-fracture electron microscopy, by using cultured epithelial cells and model organisms, including mice and fruit fly. Recent development of genome editing techniques have enabled us to perform convincing loss-of-function analyses of the proteins of our interests in cultured epithelial cells. The following are ongoing projects.
1. Molecular mechanisms of tight junctions and pathological conditions caused by their dysfunction.
2. Molecular dissection of tricellular tight junctions and elucidation of their physiological functions.
3. Physiological functions of tight junctions and the related junctional structures in vivo.
4. Roles of septate junctions in intestinal barrier function and regulation of stem cell proliferation in fruit fly.
5. Regulatory mechanisms of epithelial morphogenesis by membrane traffic
Molecular architecture and morphology of tricellular tight junctions.
Tricellular tight junctions (tTJs) are cell-cell junctions located at tricellular contacts, where the corners of three epithelial cells meet. tTJs contain two types of tTJ-specific membrane proteins, angulin family and tricellulin, and pull claudin-based tight junctions to the center of tricellular contacts.
Roles of smooth septate junctions in the Drosophila midgut.
When the expression of a smooth septate junction-associated membrane protein Ssk is suppressed in the adult Drosophila gut, the intestinal barrier function is impaired, leading to the leakage of blue dye from the intestinal lumen to the body cavity with overproliferation of enterocytes.
Selected publications
*Otani et al. J Cell Biol 218, 3372 (2019)*Izumi et al., J Cell Sci 134: jcs257022 (2021)
*Sugawara et al., J Cell Biol 220: e202005062 (2021)