プレナリーレクチャー 1 / Plenary Lecture 1

3 月 21 日 / March 21 , Sat. 10 : 00 〜 10 : 45

A 会場 / Room A
座長：廣川 信隆（ 東京大学 ）PL1Electron Tomography or the Challenge of Doing Structural Biology
in situ

Wolfgang Baumeister
Max-Planck-Institute of Biochemistry Germany

Electron cryotomography enables the structural analysis of non-repetitive pleomorphic structures,such as organelles or even whole cells providing unprecedented insights into their supramolecularorganization. In conjunction with subtomogram classiﬁcation and averaging molecular structures
can be studied, i.e. in their functional cellular environments. Recent developments suchas the targeted micromachining of cells embedded in amorphous ice using correlative LM-EMtechniques and focused ion beam technology open up new windows of opportunity for studying
cellular ultrastructure. Studies of ribosomes and proteasomes
and of neurotoxic aggregateswill illustrate the potential of this new approach to structural cell biology.

References:1)
㹒㹑Cryo-Electron Tomography: The Challenge of Doing Structural Biology In
Situ (Review). J. Cell Biol. 202, 407-19 (2013).
2)
The native 3D organization ofbacterial polysomes. Cell. 136, 261-271 (2009).
3)
Structure of hibernating ribosomes studied by cryoelectron tomographyand. J. Cell
Biol. 190, 613-621 (2010).
4)
Opening Windows into the Cell: Focused-Ion-Beam Millingfor Cryo-Electron Tomography, Current Opinion in Structural Biology 23:1-7 (2013).
5): Electron microscopy of biological materials at thenanometer scale. Ann. Rev. Mat. Sci. 42 (2012).

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プレナリーレクチャー 2 / Plenary Lecture 2

3 月 21 日 / March 21 , Sat. 10 : 45 〜 11 : 30

A 会場 / Room A
座長：久保 義弘（ 生理学研究所 ）PL2

低温電子顕微鏡を用いた構造生理学研究
Structural physiology studied by cryo-electron microscopy

藤吉 好則
名古屋大学・創薬科学研究科

Yoshinori Fujiyoshi
Cellular and Structural Physiology Institute (CeSPI) and Graduate
School of Pharmaceutical Sciences, Nagoya University, JapanI am personally interested in molecular mechanisms, how education and experiences during human development inﬂuence the ability and personality of the adult. To challenge such a diﬃcult
question, structural and functional studies of membrane proteins are important, and thus I named
this research ﬁeld structural physiology. I would like to discuss mainly three topics of cell adhesive-channels. First, as an exceptional feature speciﬁc to AQP4 among 13 water channel isoforms,
characteristic orthogonal arrays were observed and the array formation of AQP4 was regulatedby the N-terminal palmitoylation of either Cys13 or Cys17, which was revealed by structure analysis of AQP4 2D-crystals [JMB 355, 628-39 (2006)] and subsequent freeze-fracture studies [BBA1778, 1181-9 (2008)]. Large numbers of AQP4 molecules with cell adhesive-function are expressedin the glial lamellae of hypothalamus at which important brain functions such as thermo-, osmoand glucose-sensory systems are thought to be carried out. For example, AQP4 might therefore
be responsible for the pressure regulation in brain. The second topic is gap junction intercellularcommunication channels that allow a wide variety of solutes to pass through, and have criticalroles in biologically important processes, such as, cardiac development, fertility, immune systemand electrical signaling in the nervous system. The structures of connexin-26 were analyzed byelectron crystallography [PNAS, 104 10034-9 (2007)] as well as X-ray crystallography [Nature 458,597-602 (2009)], and we proposed plug gating model as a gating mechanism of the gap junction
channel. As the third topic, we recently analyzed structure of claudin by X-ray crystallography
and proposed a paracellular channel model [Science 344, 304-7 (2014)].

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プレナリーレクチャー 3 / Plenary Lecture 3

3 月 22 日 / March 22 , Sun. 10 : 30 〜 11 : 15

A 会場 / Room A
座長：東原 和成（ 東京大学 ）PL3

Receptors, Neurons, and Circuits: The Biology of Mammalian
TasteCharles S. Zuker
Howard Hughes Medical Institute and Columbia University, USA

The taste system is one of our fundamental senses, responsible for detecting and responding tosweet, bitter, umami, salty, and sour stimuli. In the tongue, the ﬁve basic tastes are mediated byseparate classes of taste receptor cells each ﬁnely tuned to a single taste quality. In the cortex,
each taste quality is represented in its own separate cortical ﬁeld, revealing the existence of agustotopic map in the brain. We study the logic of taste coding as a platform to understand how
our brain creates an internal representation of the outside world and transforms sensory signals
at the periphery into percepts, actions and complex behaviors.

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プレナリーレクチャー 4 / Plenary Lecture 4

3 月 22 日 / March 22 , Sun. 11 : 15 〜 12 : 00

A 会場 / Room A
座長：佐藤 真（ 大阪大学 ）PL4

マウス嗅覚系における神経地図形成の基本原理
Neural Map Formation in the Mouse Olfactory System坂野 仁
福井大学・医学部

Hitoshi Sakano
School of Medicine, University of Fukui, Japan

In the mouse olfactory system, odorants are detected with ~1,000 diﬀerent odorant receptor (OR)species expressed in the cilia of olfactory sensory neurons (OSNs). Each OSN in the olfactory
epithelium (OE) expresses only one functional OR gene in a mutually exclusive and mono-allelicmanner. Furthermore, OSNs expressing the same OR species converge their axons to a speciﬁclocation in the olfactory bulb (OB) forming a glomerular structure. Because a given OR responds
to multiple odorants and a given odorant activates multiple OR species, the odor information detected in the OE is topographically represented as the pattern of activated glomeruli in the OB1).
A remarkable feature of axonal projection in the mouse olfactory system is that ORs play aninstructive role in projecting OSN axons to the OB. For dorsal-ventral (D-V) projection, anatomical location of OSN cells within the OE regulates both OR gene choice and expression levels ofaxon guidance molecules, thus indirectly correlating the OR identity to the glomerular location
along the D-V axis2). In contrast, anterior-posterior (A-P) projection is totally independent of thepositional information of OSN cells, but instead dependent on the expressed OR species3). We haverecently found that A-P targeting is regulated by the agonist-independent baseline activity of ORsusing cAMP as a second messenger4). OR-derived cAMP signals also regulate the expression ofglomerular segregation molecules for the map reﬁnement through local sorting of OSN axons5).
Unlike A-P projection molecules, glomerular segregation molecules are regulated by stimulusdriven neuronal activity4).
Here, we discuss the recent progress in the neural map and circuit formation in the mouse olfactory system.
References
1) Mori, K. and Sakano, H.:
2) Takeuchi, H., et al.:141, 1056 (2010).
3) Imai, T., et al.:
325, 585 (2009).
4) Nakashima, A., et al.:154, 1314 (2013).
5) Serizawa, S., et al.:127, 1057 (2006).

34, 465 (2011).

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プレナリーレクチャー 5 / Plenary Lecture 5

3 月 23 日 / March 23 , Mon. 10 : 30 〜 11 : 30

A 会場 / Room A
座長：内山 安男（ 順天堂大学 ）PL5

酵母によるオートファジーの分子機構
Molecular Dissection of Autophagosome Formation in Yeast

大隅 良典
東京工業大学・フロンティア研究機構

Yoshinori Ohsumi
Integrated Research Institute, Tokyo Institute of Technology, Japan

Autophagy is well a conserved degradation process of cytoplasmic constituents in the lysosome/vacuole. Recently it is getting clear that autophagy plays important roles in so many physiological events and is related to diseases. More than 26 years ago we ﬁrst found autophagy in yeast
induced by nutrient starvations by light microscopic observation. Taking advantage of the yeast
system, we started genetic approach to dissect the process, and successfully isolated many autophagy-defective mutants. Subsequent identiﬁcation of ATG genes revealed unique set of genes
involved in membrane dynamics during autophagy. These genes were mostly conserved in mammals and plants and most other eukaryotes. These ﬁndings triggered a vast of autophagy researchin various organisms. We know now that 18genes are essential for starvation-induced
autophagy in yeast. They consist of six functional units, namely the Atg1 protein kinase and its
regulators, the PI3 kinase complex, the Atg2-Atg18 complex, the membrane protein Atg9, and two
unique ubiquitin-like conjugation systems. Then we have been focusing to elucidate the structureand function of each Atg protein. Atg proteins function concertedly in membrane dynamics during the formation of autophagosome. Recent studies on the Atg proteins, especially early steps of
the PAS assembly will be presented. In addition recent physiological roles of autophagy in yeast
will be discussed.

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大会企画学術教育講演 1 / Academic Education Lecture 1

3 月 21 日 / March 21 , Sat. 14 : 00 〜 14 : 45

A 会場 / Room A
座長：久場 博司（ 名古屋大学 ）EL1

生命の要、モーター分子群、KIFs と細胞内輸送：
記憶・学習及び発生の制御から疾患まで
Kinesin Superfamily Molecular Motors, KIFs: Intracellular Transport, Regulation ofHigher Brain Function, and Development and Diseases

廣川 信隆
東京大学・医学系研究科

Nobutaka Hirokawa
Graduate School of Medicine, The University of Tokyo, Japan

神経細胞を初めとする全ての細胞内で多くの蛋白質は、様々な膜小胞や蛋白複合体として直径25nm の微小管の上を、特定の方向へ異なる速度で輸送される。この輸送機構は、細胞の機能や形作りに必須であり、その主役は、微小管上を様々な荷物（cargo）を輸送するモーター分子である。
私達は、哺乳類（ヒト、及びマウス）のモーター分子群、Kinesin superfamily proteins（ KIFs）の遺伝子 45 個を全て同定し、細胞内輸送機構を解明してきた。すなわち、各々の KIFs のカーゴ、輸送の方向性と速度、KIF によるカーゴの認識、目的地でのカーゴの乖離、そして異なる方向への輸送の機構を明らかにした。
さらに個体レベルでの各々の KIF の働きを解明する為、transgenic mouse, knockout mouse の作成と解析を行った。この解析を通して、多種類の KIF が、記憶・学習などの高次脳機能や、脳の回路網の形成、活動依存性の神経細胞の生と死、神経の分化増殖の制御や、腫瘍の抑制あるいは、私たちの体の左右非対称性の決定などの重要な生命現象を司っているという驚くべき事実が明らかになり、さらに、KIFs の障害により、神経変性症、癲癇、不安神経症、水頭症、女性不妊、腫瘍、糖尿病等の疾患が起こる事も明らかとなった。さらに Cryo EM, X‑ 線結晶解析、生物物理学を駆使して KIFの動く機構を明らかにした。

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大会企画学術教育講演 2 / Academic Education Lecture 2

3 月 21 日 / March 21 , Sat. 14 : 45 〜 15 : 30

A 会場 / Room A
座長：野田 泰子（ 自治医科大学 ）EL2

1 分子から階層を超えて生体システムにつなぐ統合的研究
Integrative research on bio-system bridging from single molecules to organ

柳田 敏雄
大阪大学・生命機能研究科

Toshio Yanagida
Graduate School of Frontier Biosciences, Osaka University, Japan

現在生命科学は飛躍的に進歩している。特に、蛋白質や遺伝子など生体分子の計測解析技術が大きく発展し、膨大なデータが得られている。問題は、これら分子レベルのデータを如何に統合してシステム、すなわち個体や臓器の生理機能につなぐかである。しかし、生体システムはあまりにも複雑でいろいろな要素が絡み合っているので、極めて難問である。最近、理研の 10 ペタ Flops（ 1 秒間に 10の 15 乗回の演算）スパコン “ 京 ” が使えるようになり、少し可能性がでてきた。我々は、1 分子計測で得られたミオシン分子モータの実験データを基に、私がリーダーをしている計算機の生物応用プロジェクトに参加している久田グループが開発した UT-Heart シミュレータでスパコン “ 京 ” の中に筋肉と心臓を再現し、ミオシン分子の性質やその変異が心臓の拍動にどのような影響をあたえるかを調べている。講演では、収縮タンパク分子の変異と心臓拡張症などの病気との関係についても説明する。
これとは対照的に、トップダウン的アプローチで脳機能に迫る研究についても述べる。

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生理学会特別講演 萩原生長記念レクチャー / S. Hagiwara Memorial Lecture

3 月 23 日 / March 23 , Mon. 13 : 30 〜 14 : 15

A 会場 / Room A
座長：藤田 一郎（ 大阪大学 ）NL1

大脳 MT/MST 野による眼球運動の制御
The role of cortical areas MT/MST in short-latency ocular tracking

河野 憲二
京都大学・医学研究科

Kenji Kawano
Graduate School of Medicine, Kyoto University, Japan

Whenever we move around in the environment, the observerʼs movements activate the vestibularorgans and are then compensated by the vestibulo-ocular reﬂexes (VORs). However, the VORs
are not always perfect and the visual acuity is severely impaired if the images of interest on theretina move excessively. Recent studies revealed three distinct visual tracking eye movementswith ultra-short latencies (~60 ms in monkeys), which are thought to help reduce the residualvisual disturbances. One of these eye movements is ʻocular followingʼ, which deals with the visualstabilization problems confronting the observer who looks oﬀ to one side. Two other eye movements, ʻdisparity vergenceʼ and ʻradial-ﬂow vergenceʼ, deal with the binocular fusion problems of
the observer who looks in the direction of heading.
To understand the neural mediation of these tracking eye movements, we focused on the role ofthe middle temporal (MT) and medial superior temporal (MST) areas within the superior temporal sulcus (STS) of the monkeyʼs cortex, since these areas are known to contain many neurons
that respond vigorously to visual motion with directional selectivity and others that are sensitive
to binocular disparity or to the patterns of optic ﬂow experienced by the moving observer. We
recorded single unit activities and made focal chemical lesions in these areas in monkeys. The
results were consistent with the hypothesis that the MT/MST areas are primary sites for initiating all three visual tracking eye movements at ultra-short latencies.

59生理学会特別講演 田原淳記念レクチャー / S. Tawara Memorial Lecture

3 月 23 日 / March 23 , Mon. 14 : 15 〜 15 : 00

A 会場 / Room A
座長：松田 博子（ 関西医科大学 ）NL2

横紋筋における細胞内 Ca2+；測定と生理学的意義
Intracellular Ca2+ in striated muscle: measurement and physiological significance栗原 敏
東京慈恵会医科大学

Satoshi Kurihara
The Jikei University School of Medicine, Japan

Intracellular Ca ion (Ca2+) plays a pivotal role in muscle contraction. In the present Tawara Memorial Lecture, I will present the intracellular Ca2+ concentration change measured with the Ca2+
sensitive photoprotein aequorin in mammalian cardiac muscles, and will discuss the molecularmechanism of the length-dependent change of tension in cardiac muscle (the Frank-Starling law of
the heart). If the papillary muscle of the rat or ferret was stretched from a shorter length to thelength to produce maximal tension (Lmax), tension was increased without a change in the peakCa2+ signal (Ca2+ transient, CaT). However, the relaxation time was prolonged and the decay timeof CaT was shortened. If muscle length was quickly shortened from Lmax to a shorter length
during a twitch contraction, tension was promptly decreased and then re-developed. In response
to quick release, the CaT showed a transient increase (hump) in the falling phase. The magnitudeof the hump was correlated with the magnitude of tension reduction rather than with muscle
length. If the preparation was treated with 2,3-butanedione monoxime, tension disappeared, butthe CaT was not greatly aﬀected. In the 2,3-butanedione monoxime-treated preparation, quick
release did not induce a hump in the CaT. Thus, the change in muscle length aﬀects the Ca2+ afﬁnity of the Ca2+-binding protein troponin through cross-bridge attachment and detachment. The
measurement of the intracellular Ca2+ concentration is essential for understanding the molecularmechanism of cardiac muscle contraction.

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