Associate Professor Takeda Tetsuya
Group research activities
Project: Membrane remodeling in health and disease(1) Elucidating membrane fission mechanisms by DynaminEndocytosis is required for incorporation of molecules from extracellular environment into cells
across membrane barrier. Endocytosis is required for essential biological processes including
differentiation, neuronal transduction and signal transduction. In contrast, aberrant endocytosis
is tightly linked to various congenital diseases and cancers. Thus, studying endocytosis isimportant for both physiological and pathological perspectives. In endocytosis, a small area ofcell membrane is invaginated and severed to form endocytic vesicles. Dynamin, a large GTPase,
plays essential roles in the membrane invagination and fission (membrane remodeling) inendocytosis. Dynamin assembles into an higher ordered “helical” structure at the neck ofinvaginating endocytic pits and structuralchanges of the helices coupled with GTP
hydrolysis drives membrane fission. However,precise mechanisms of the dyamin-mediatedmembrane fission remain to be elucidated. We
are analyzing mechanism of thedynamin-mediated membrane fission using
High Speed Atomic Force Microscopy(HS-AFM) to tackle this fundamental
question (Fig.1).
(2) Pathogenesis of congenital myopathy caused by aberrant membrane
remodeling
Congenital myopathies are a group ofmuscle diseases causing muscular weakness.
Althoughfrequencyofcongenital

myopathies is relatively low (e.g. 1000
patients in Japan), its pathogenesis is poorly
understood thus designated as one of rare
intractable diseases by Japanese Ministry ofHealth, Labour and Welfare. Centronuclear myopathy (CNM) is one of congenital myopathies
and membrane remodeling proteins, Dynamin2 and BIN1, are among causal genes of CNM. We
hypothesize that membrane remodeling defects caused by mutations of Dynamin2 and BIN1
leads to pathogenesis of CNM. To elucidate pathogenesis of CNM, we are taking
multidisciplinary approaches including cell biology, genetics, biochemistry and biophysics
using muscle cell lines and in vitro reconstituted system (Fig.2).
(3) Membrane remodeling in cytokinesis
Cytokinesis is the final step in cell division that physically separates one mother cell into two
daughter cells. Regulated cytokinesis is crucial to guarantee proper inheritance of genomic
materials into daughter cells. In the development of animals and plants, asymmetrical separationof cell fate determinants is essential for cell differentiation. In contrast, aberrant cytokinesis
causes various diseases such as cancer, infertility and developmental defects. Cytokinesis isaccompanied by a dynamic morphological changes of cell shape, which is caused bycooperative function of cytoskeleton (actin and microtubules) and membrane. Although
function and regulation of cytoskeleton in cytokinesis is relatively well understood, membrane
function remains to be elucidated. We have demonstrated membrane remodeling machineries,
BAR domain proteins and ESCRT, playessential roles in membrane function incytokinesis (Takeda et al., Nat. Cell Biol.
2004; Takeda et al., Open Biol. 2013;
Capalbo et al., Open Biol. 2012). We aretaking multiple approaches including cellbiology, in vitro reconstitution and live
imaging to elucidate function and regulationof membrane remodeling in cytokinesis.

Selected Pub lications
Takeda, T., Robinson, I.M., Savoian, M.M., Griffiths, J.R., Whetton, A.D., McMahon, H.T. andGlover, D.M. (2013) Drosophila F-BAR protein Syndapin contributes to coupling theplasma membrane and contractile ring in Cytokinesis. Open Biol. 7;3(8):130081.
(http://rsob.royalsocietypublishing.org/content/3/8/130081/suppl/DC2)
Capalbo, L. Montembault, E., Takeda, T., Bassi, ZI., Glover, D.M., D’Avino, P.P. (2012) The
chromosomal passenger complex controls the function of endosomal sorting complex

required for transport-III Snf7 proteins during cytokinesis. Open Biol. 2(5):120070.
Takeda, T., Chang, F. (2005) Role of fission yeast myosin I in organization of sterol-richmembrane domains. Curr Biol. 15(14):1331-6.
Takeda, T., Kawate, T., Chang, F. (2004) Organization of a sterol-rich membrane domain by
Cdc15p during cytokinesis in fission yeast. Nat Cell Biol. 6(11):1142-4.
Zhang, Y., Nolan, M., Yamada, H., Watanabe, M., Nasu, Y., *Takei, K. and *Takeda, T.
(*Corresponding author) Dynamin2 GTPase contributes to invadopodia formation ininvasive bladder cancer cells. Biochem. Biophis. Res. Commun., 2016; 480: 409-414.

Other publicatoins
竹田哲也（2016）細胞質分裂における膜ダイナミクスの機能、生物物理 56 (１),013-017.

Yamada, H., Takeda, T., Michiue, H., Abe, T. and Takei, K. Actin bundling by dynamin 2 andcortactin is implicated in cell migration by stabilizing filopodia in human non-small lungcaricinoma cells. Int J Oncol., 2016; 49(3):877-886.
Yamada H, Kobayashi K, Zhang Y, Takeda T, Takei K. Expression of a dynamin 2 mutant
associated with Charcot-Marie-Tooth disease leads to aberrant actin dynamics andlamellipodia formation. Neurosci Lett. 2016 Aug 15;628:179-85.
Yamada, H., Kikuchi, T., Masumoto, T., Fan-Yan Wei, F-Y., Abe, T., Takeda, T., Nishiki, T.,
Tomizawa, K., Watanabe, M., Matsui, H. and Takei, K. Possible role of cortactin
phosphorylation by protein kinase Cα in actin-bundle formation at growth cone. Biol.
Cell, 2015; 107: 1-12.
D’Avino, P.P., Takeda, T., Capalbo, L., Zhang, W., Lilley, K., Laue, E. and Glover, D.M.
(2008) Interaction between Anillin and RacGAP50C connects the actomyosin contractile
ring with spindle microtubules at the cell division site. J. Cell Sci. 121(Pt 8):1151-8.
Glover, D.M., Capalbo, L., D'Avino, P.P., Gatt, M.K., Savoian, M.S. and Takeda, T. (2008)
Girds ‘n’ Cleeks o’ Cytokinesis: microtubule sticks and contractile hoops in Drosophilacell division. Biochem Soc Trans. 2008 Jun;36(Pt 3):400-4.
Yonetani, A, Lustig, RJ., Moseley, J., Takeda, T., Goode, BL. and Chang, F. (2008) Regulationand targeting of the fission yeast formin cdc12p in cytokinesis. Mol. Biol. Cell 2008
May;19(5):2208-19.
Noguchi E, Iwama A, Takeda K, Takeda T, Kamioka M, Ichikawa K, Akiba T, Arinami T,Shibasaki M. (2003) The promoter polymorphism in the eosinophil cationic protein geneand its influence on the serum eosinophil cationic protein level. Am J Respir Crit CareMed., 167(2):180-4.
Ueno H, Gonda K, Takeda, T., Numata O. (2003) Identification of elongation factor-1alpha as aCa2+/calmodulin-binding protein in Tetrahymena cilia. Cell Motil Cytoskeleton.
55(1):51-60.
Takeda, T., Yoshihama, I., Numata, O. (2001) Identification of Tetrahymena Hsp60 as a 14-nmFilament Protein/Citrate Synthase-Binding Protein and Its Possible Involvement in theOral Apparatus Formation. Genes to Cells 6 (2), 132-149.
Numata, O., Hanyu, K., Takeda, T., Watanabe, Y. (1998) Tetrahymena calcium-binding proteins,
TCBP-23 and TCBP-25. In Tetrahymena thermophila, ed. By D.J. Asai and J.D. Forney,
Methods in Cell Biology 62, 455-465.
Takeda, T., Watanabe, Y., Numata, O. (1997) Direct Demonstration of the Bifunctional
Property of Tetrahymena 14-nm Filament Protein/Citrate Synthase Following Expressionof the Gene in Escherichia coli. Biochem.Biophis.Res.Commun. 237, 205-210.
Takeda, T., Kurasawa, Y., Watanabe, Y., Numata, O. (1995) Polymerization of Highly PurifiedTetrahymena 14-nm Filament Protein/Citrate Synthase into Filaments and Its Possible
Role in Regulation of Enzymatic Activity. J.Biochemistry 117, 869-874.