Ikenouchi Lab

Epithelial Cell Biology

In the textbooks, cell membranes are described as “gray two lines”. But actually, cells make many different lipid species.　Although lipids are the main component of cells together with proteins, the functions of lipids or the physiological meaning of diversity of lipid species are not well elucidated.

Membrane model of Singer & Nicolson (1972)

The aim of our study from the viewpoint of basic science is to clarify the roles of individual lipid species by using epithelial polarity and cell adhesion as experimental systems. The research purpose for clinical science is to find novel therapeutic targets in diseases correlated with epithelial-polarity disorders and epithelial-mesenchymal transition, such as cancer, polycystic kidney disease and pulmonary fibrosis.

Research

Epithelial cells are constitutively polarized to play fundamental functions such as vectorial transport. There are two membrane domains of epithelial cells, the apical membrane and basolateral membrane. These membrane domains are separated by cell adhesion apparatus. Most of our previous studies concerning epithelial polarity and cell adhesion have been focused on identification of new genes or elucidation of protein-protein interactions（for example, tricellulin of FRMD4A)

Although lipids are the main component of cells together with proteins, the functions of lipids or the physiological meaning of diversity of lipid species are not well elucidated. To analyze membrane lipids, we recently developed a new method to determine the lipid composition of plasma membrane (Ikenouchi et al. 2012).Taking advantage of this method, we succeeded in clarifying the difference of lipid composition between the apical membrane and the basolateral membrane and found that sphingomyelin plays essential roles in the formation of microvilli (Ikenouchi et al. 2013).

Furthermore, we identified several epithelial-cell specific lipids by comparing the lipid profile between epithelial cells and mesenchymal cells, taking advantage of previously established cell lines (Ikenouchi et al.2003).Currently we try to elucidate functional roles of these lipids by examining whether knock-down of biosynthetic enzymes in cultured epithelial cells affect epithelial polarity and cell-cell adhesion.

The aim of our study from the viewpoint of basic science is to clarify the importance of individual lipid species by using epithelial cells as an experimental model. The research purpose for clinical science is to find novel therapeutic targets in diseases correlated with epithelial-polarity disorders and epithelial-mesenchymal transition, such as cancer, polycystic kidney disease and pulmonary fibrosis.

Elucidation of roles of lipids in the formation of epithelial polarity and cell adhesion
Elucidation of the organizing principles of living cell membrane by combining synthetic biological approaches and cell biological approaches

Members

Junichi Ikenouchi

Professor M.D., Ph.D.　 [Bio]

Lecuturer　

Kenji Matsuzawa Ph.D.

Assistant Professor　

Kenta Shigetomi Ph.D.

Atsushi Matsumoto Ph.D.

JSPS Postdoctoral Fellowship　

Saya Okada Ph.D.

Technical Assistant　

Sawako Watanabe

Yuma Cho

Junichiro Imamura, Yuki Fujii

Yuki Maekawa, Asahi Yokozaki

Takato Iwata, Soohee Shin

Yuki Kikuchi, Yuta Takahashi, Kento Tsuruzoe, Naoya Fuse

Lab photos
Recent photos are uploaded to Facebook page.

Publication

Recent Publications　 [More]

(† : Corresponding author)
(* : Co-first author)

Tanaka T, Matsumoto A, A S Klymchenko, Tsurumaki E, † Ikenouchi J, † Konishi G.
Fluorescent Solvatochromic Probes for Long-Term Imaging of Lipid Order in Living Cells
Adv Sci. 2024 Mar 11:e2309721. [Pubmed]

Fujii Y, †Ikenouchi J.
Cytoplasmic zoning in membrane blebs
J Biochem. 2024 Feb 25;175(2):133-140. [Pubmed]

Ito S, Kuromiya K, Sekai M, Sako H, Sai K, Morikawa R, Mukai Y, Ida Y, Anzai M, Ishikawa S, Kozawa K, Shirai T, Tanimura N, Sugie K, Ikenouchi J, Ogawa M, Naguro I, Ichijo H, †Fujita Y.
Accumulation of annexin A2 and S100A10 prevents apoptosis of apically delaminated, transformed epithelial cells
Proc Natl Acad Sci U S A. 2023 Oct 24;120(43):e2307118120. [Pubmed]

Shigetomi K, Ono Y, Matsuzawa K,†Ikenouchi J.
Cholesterol rich domain formation mediated by ZO proteins are essential for tight junction formation
Proc Natl Acad Sci U S A. 2023 Feb 21;120(8):e2217561120. [Pubmed]

Ono Y, Matsuzawa K,† Ikenouchi J.
mTORC2 suppresses cell death induced by hypo-osmotic stress by promoting sphingomyelin transport
J Cell Biol. 2022 Apr 4;221(4):e202106160. [Pubmed]

Cho Y, Haraguchi D, Shigetomi K, Matsuzawa K, Uchida S,† Ikenouchi J.
Tricellulin secures the epithelial barrier at tricellular junctions by interacting with actomyosin
J Cell Biol. 2022 Apr 4;221(4):e202009037. [Pubmed]

†Ikenouchi J, Aoki K.
A Clockwork Bleb: cytoskeleton, calcium, and cytoplasmic fluidity
FEBS J. 2021 Oct 6;16220.[Pubmed]

Matsuzawa K, Ohga H, Shigetomi K, Shiiya T, Hirashima M,† Ikenouchi J.
MAGIs regulate aPKC to enable balanced distribution of intercellular tension for epithelial sheet homeostasis
Commun. Biol. 2021 Mar 12;4(1):337.[Pubmed]

Aoki K, Harada S, Kawaji K, Matsuzawa K, Uchida S, †Ikenouchi J.
STIM-Orai1 signaling regulates fluidity of cytoplasm during membrane blebbing.
Nat Commun. 2021 Jan 20;12(1):480.[Pubmed]

Aoki K, Satoi S, Harada S, Uchida S, Iwasa Y, †Ikenouchi J.
Coordinated changes in cell membrane and cytoplasm during maturation of apoptotic bleb.
Mol Biol Cell. 2020 Feb 12:mbcE19120691.[Pubmed]

Shigetomi K, †Ikenouchi J.
Cell Adhesion Structures in Epithelial Cells Are Formed in Dynamic and Cooperative Ways.
Bioessays. 2019 Jul 41(7):e1800227.[Pubmed]

†Ikenouchi J.
Roles of membrane lipids in the organization of epithelial cells: Old and new problems.
Tissue Barriers. 2018 Aug 29:1-8.[Pubmed]

Matsuzawa K,Himoto T,Mochizuki Y, †Ikenouchi J.
α-Catenin Controls the Anisotropy of Force Distribution at Cell-Cell Junctions during Collective Cell Migration.
Cell Rep. 2018 Jun 19;23(12):3447-3456.[Pubmed]

Tsuchiya M, Hara Y, Okuda M, Itoh K, Nishioka R, Shiomi A, Nagao K, Mori M, Mori Y, Ikenouchi J, Suzuki R, Tanaka M, Ohwada T, Aoki J, Kanagawa M, Toda T, Nagata Y, Matsuda R, Takayama Y, Tominaga M, †Umeda M.
Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation.
Nat Commun. 2018 May 24;9(1):2049.[Pubmed]

Shigetomi K, Ono Y, Inai T, †Ikenouchi J.
Adherens junctions influence tight junction formation via changes in membrane lipid composition.
J Cell Biol. 2018 May 2.doi:10.1083.[Pubmed]

Kinoshita M, Ano H, Murata M, Shigetomi K, Ikenouchi J, †Matsumori N.
Emphatic visualization of sphingomyelin-rich domains by inter-lipid FRET imaging using fluorescent sphingomyelins.
Sci Rep. 2017 Dec 1;7(1):16801.[Pubmed]

Shigetomi K, †Ikenouchi J.
Regulation of the epithelial barrier by post-translational modifications of tight junction membrane proteins.
J Biochem. 2017 Nov 24. doi: 10.1093/jb/mvx077[Pubmed]

Nishimura T, Ito S, Saito H, Hiver S, Shigetomi K, Ikenouchi J, †Takeichi M.
DAAM1 stabilizes epithelial junctions by restraining WAVE complex-dependent lateral membrane motility.
J Cell Biol. 2016 Nov 21;215(4):559-573. [Pubmed]

†Ikenouchi J.
How do cells sense actin cortex-free membrane?
Cell Cycle. 2016 Oct 17;15(20):2687-8. [Pubmed]

†Ikenouchi J, Aoki K.
Membrane bleb : a seesaw game of two small GTPases.
Small GTPases. 2016 [Pubmed] (Review)

Aoki K, Maeda F, Nagasako T, Mochizuki Y, Uchida S, and †Ikenouchi J.
A RhoA and Rnd3 cycle regulates actin reassembly during membrane blebbing
Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):E1863-71. [Pubmed]

*Shiomi R, *Shigetomi K, Inai T, Sakai M, †Ikenouchi J.
CaMKII regulates the strength of the epithelial barrier.
Sci Rep. 2015 Aug 18;5:13262. [Pubmed]

Arita Y, Nishimura S, Ishitsuka R, Kishimoto T, Ikenouchi J, Ishii K, Umeda M, Matsunaga S, Kobayashi T, †Yoshida M.
Targeting cholesterol in a liquid-disordered environment by theonellamides modulates cell membrane order and cell shape.
Chem Biol. 2015 May 21;22(5):604-10. [Pubmed]

Ohoka A, Kajita M, Ikenouchi J, Yako Y, Kitamoto S, Kon S, Ikegawa M, Shimada T, Ishikawa S, †Fujita Y.
EPLIN is a crucial regulator for extrusion of RasV12-transformed cells.
J Cell Sci. 2015 Feb 15;128(4):781-9. [Pubmed]

Oda Y, Otani T, Ikenouchi J, †Furuse M.
Tricellulin regulates junctional tension of epithelial cells at tricellular contacts through Cdc42.
J Cell Sci. 2014 Oct 1;127(Pt 19):4201-12. [Pubmed]

†Ikenouchi J, Hirata M, Yonemura S, Umeda M.
Sphingomyelin clustering is essential for the formation of microvilli.
J Cell Sci. 2013 Aug 15;126(Pt 16):3585-92. [Pubmed]

Recruitment

We are in the recruitment of graduate students, postdoctoral and research assistant.

Contact

Kyushu University, Department of Cell Biology, Faculty of Sciences Professor
Junichi Ikenouchi M.D., Ph.D.
TEL: +81-92-802-4292
E-mail: ikenouchi.junichi.033(at-mark)m.kyushu-u.ac.jp

West 1st Building W1-D-809, 744 Moto-oka Nishi-ku Fukuoka