Research Introduction

organisms and essential for maintenance of the membrane potential might have developed the gliding mechanism of ... in Microbiology. 29, 15-21. PMID: ...

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OCARINA Communication 5

OCARINA Communication 5

■Research Introduction

■Research Introduction Professor, Graduate School of Science, OCU

Professor, Graduate School of Science, OCU

Completed a doctorate in science at Department of Biology, Faculty of Science, Osaka Univ. in Mar 1988. Research Associate at Department of Biology, Faculty of Science, Osaka City Univ, Apr 19 8 8 - Spt 19 95. Visiting S cholar at Har vard University, Mar 2000-Mar 2001. PRESTO JST re s e a rc h e r O c t 2 0 0 3 - A p r 2 0 07. Le a d e r o f Grand-in-Aid for Scientific Research on Innovative Areas "Harmonized supramolecular motility machinery and its diversity", from The Ministry of Education, Culture, Sports, Science and Technology (MEXT). July 2012-Mar 2017 Current position since October 2006.

Completed a doctorate course at the Graduate S c h o o l o f S c i e n c e , O C U i n M a r c h 19 8 9 . Received a professorship at OCU in April 2006 af ter conducting research as a fellow of the Japan Society for the Promotion of Science, and holding positions as a research scientist at the S c i e n c e a n d Te c h n o l o g y A g e n c y ( R I K E N ), as sistant (education) at Oita Universit y and assistant (science) and assistant professor at Kyoto University. Became a researcher at the R e s e a rc h C e nte r fo r S c i e n c e S y s te m s , t h e Japan Society for the Promotion of Science in April 2013 (concurrent post).

Makoto Miyata How motility is developed repeatedly!?

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Many organisms can move. At first glance, the motility mechanism seems diverse. However, we understand that almost all organisms including human being have the com mon mecha n ism of mot i l it y when we t race t he mechanism. Namely, conventional motor proteins, Myosin, K i nesi n , D y nei n gl ide on ra i l protei n ba sed on t he hydrolysis energy of ATP. Numerous prominent researches have been conducted about the process of force generation and we got considerable understanding of the mechanism. However, based on the recent progress of genomic analysis and visualizing technology, it is becoming clear that many intrinsically different mechanisms of motility exist. I am in charge of the project, "Harmonized supramolecular motility machinery and its diversity", a Grant-in -Aid for Scientific Research on innovative Areas from Ministry of Education, Culture, Sports, Science and Technology in Japan. In our project, we are trying to clarify the mechanism of motility to atomic level. We think that the understanding of various mot i l it y mech a n isms lead to t he u nder st a nd i ng of organisms themselves. Furthermore, it leads to methods to control organisms critical for medicine and industry.  In Osaka City University, we offer the technological development and analysis of "Quick freeze replica electron microscopy method (which is useful but to be lost as it stands)" and the analysis of mass spectrometry, as the generic support for the proposed research area, to the approximately 50 research area- groups throughout Japan. Besides , we study the motility mecha nisms of class Mollicutes which is a group of pathogenic bacteria, as the role of research team at Osaka City University.  The class Mollicutes is a class of bacteria, Low- GC branch of Gram-positive bacteria which evolved in unique ways through parasitic life cycle in higher animals and plants. They threw away their cell wall and tail (in other words, peptidoglycan and flagellum) which are to be the targets of host immune system, and then obtained a soft and light body. Furthermore, they obtained a method of camouflage and three separate unique motility mechanisms in order to escape from immune system thoroughly. We have studied these three motility mechanisms of class Mollicutes since 1997 and the research is about to reach its

climax before long. We published the proposal that the accidental contact of adhesin, common in most pathogenic microorga nisms a nd ATP synthetase, existing in a ll organisms and essential for maintenance of the membrane potential might have developed the gliding mechanism of Mycoplasma mobile, a freshwater-fish pathogen. (The below figure is the magnified image of the gliding machinery of Mycoplasma mobile. Upper blue structure like a string of beads originated from ATP synthetase. The cell inside is colored light pink. Lower surface is the solid surface like glass. The force is transmitted from (i) to (iii) in this order. 【References】Miyata M and Hamaguchi T (2016), Prospects for the gliding mechanism of Mycoplasma mobile. Current Opinion i n M icrobiolog y. 2 9 , 15 - 21 . PM I D : 2 6 5 0 018 9 . doi:10.1016/j.mib.2015.08.010. Nakane D, Kenri T, Matsuo L, and Miyata M (2015), Systematic structura l a na lyses of attachment orga nelle in Myco pl a sm a pneumoniae. PLoS Pathogens. 11, e10 05299. PMID: 266335 4 0. doi: 10.1371/journal.ppat.1005299

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Akihisa Terakita Molecular basis for animal photoreception and its optogenetics application Humans obtain more than 80% of external information through vision. Visual photoreception starts with light absorption by the photosensitive proteins, visual pigments, which exist densely in the retina of the eye. In many types of ver t ebrat e s , t he v isu a l pig ment-rel at ed prot ei n (rhodopsins) are also found in extraocular tissues and organs, such as the brain and skin, suggesting rhodopsins are involved in functions other than vision (nonvisual functions) such as light-regulation of biological rhythm. In humans, some types of rhodopsins express in the brain. They are attracting attention, although their functions have not been clear. We have studied the molecular basis and functions of extraocular photoreception and nonvisual photoreception. Our previous studies have revealed that several kinds of nonvisual rhodopsins have some properties that support extraocular photoreceptive function in various animals. [1, 2]  Re c ent ly, t he met ho d of genet ic a l ly i nt ro duci ng photosensitive proteins into neurons and controlling their activities by light has become widely used. This method is attracting attention as optogenetics. In the conventional methods of optogenetics, a kind of microbial rhodopsin, which is a light-activated ion channel, is introduced into neuron, and the neuronal activities (membrane potential cha nge,“outlet”) are controlled by light (see fig ure). Meanwhile, animal rhodopsins are G protein- coupled receptors, which light-dependently activate G proteins, signal transduction molecules. Animal rhodopsins have the potential to control the activities of various cells in addition to neurons, by controlling the“inlets”of the cells; therefore it is expected to become a new tool in optogenetics. [3] The animal rhodopsin binds to 11-cis retinal, a special isomeric chromophore, which is generated by enzymes in the eye a nd related orga ns . Because 11- cis ret i na l does not abundantly exist outside the eyes, animal rhodopsins used to be regarded as inappropriate for optogenetics.  Some types of“extraocular”rhodopsins, which we have r e c e nt ly i d e nt i fi e d , h ave pr o p e r t i e s a d e q u at e for “extraocular”functions: in contrast to vertebrate visual rhodopsins, which can absorb light only once,“extraocular” rhodopsins revert to their original dark state when they

re c eive f u r t her l ig ht , a nd t herefore m a i nt a i n s it s photosensitivity. As an example, due to this property, one of animal rhodopsins, parapinopsin, which localizes to the photo sensit ive pi nea l org a ns i n t he bra i n of lower vertebrates, activate G proteins in response to UV light, a nd stops act ivat ion immediately a fter visible light absorption. [4, 5] Also, another type of animal rhodopsins, invertebrate Opn3, functions by binding to 13-cis retinal chromophore, which exists throughout animal bodies. These types of animal rhodopsins are expected to become effective tools in optogenetics. [6] In addition, some types of rhodopsin with unique properties have been identified in various invertebrates, and are also expected to become optogenetic tools. [7, 8] 1) Terakita A & Nagata T, Zoolog. Sci. 31, 653-659 (2014) 2) Koya n ag i M & Tera k it a A , Bio ch i m . Biophy. Act a 18 3 7, 710-716 (2014) 3) Terakita A et al., In Optogenetics ed. Yawo H et al., pp77-88, Springer (2015) 4) Koyanagi M et al., Proc. Natl. Acad. Sci. USA. 101, 6687- 6691 (2004) 5) Kawano-Yamashita E et al., PLoS One. 10, e0141280 (2015) 6) Koyanagi M. et al., Proc. Natl. Acad. Sci. USA. 110, 4998-5003 (2013) 7) K o y a n a g i M . e t a l . , P r o c . N a t l . A c a d . S c i . U S A . 1 0 5 , 15576-15578 (2008) 8) Nagata et al., Science 335, 469-471 (2012)

Stimuli Hormone, neurotransmitter, sapid substance, smell substance, pheromone, etc. Animal rhodopsin (GPCR) Cell

Microbial rhodopsin (channel ) Membrane potential change (neuron, brain.)

G protein Signal transduction

Gene Enzyme Hormone expression activity secretion (liver, muscle, brain, etc.)

Fig: Outline of the optogenetic control of cells using animal rhodopsins

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