一般口演（Oral）

Oral Spine regulation 一般口演スパイン制御

7月26日（金）9:30～9:45　第9会場（朱鷺メッセ　3F　306+307） 2O-09m2-1 Specific depletion of the motor protein KIF5B leads to deficits in dendritic transport, synaptic plasticity and memory Kwok-On Lai（Lai Kwok-On）¹，Junjun Zhao（Zhao Junjun）¹，Hiu-Ka Albert Fok（Fok Hiu-Ka Albert）¹，Ruolin Fan（Fan Ruolin）¹，Hei-Lok Jonathan Chan（Chan Hei-Lok Jonathan）¹，Hoi Ying Louisa Lo（Lo Hoi Ying Louisa）¹，Wing-Ho Yung（Yung Wing-Ho）²，Jiandong Huang（Huang Jiandong）¹，Sau-Wan Cora Lai（Lai Sau-Wan Cora）¹ ¹The University of Hong Kong ²Chinese University of Hong Kong Kinesin and dynein superfamily of proteins are microtubule-dependent molecular motors that mediate long-distance transport of materials in neuron. The kinesin superfamily is very diverse and contains 45 members in mammal. One key question that is not well-addressed is whether and how the different kinesin motors exhibit functional specificity. Gene duplication and subsequent diversification give rise to three homologous kinesin I proteins (KIF5A, KIF5B and KIF5C) in vertebrates. They were initially regarded to be functionally redundant because of their conserved cargo-binding domains, but specificity between KIF5A and the other two KIF5s has been reported in axonal transport in zebrafish. Previous studies on KIF5s have mostly focused on axonal transport, while the roles of kinesin I in dendritic transport and postsynaptic function are less well-defined. Here we show that acute knockdown of KIF5A or KIF5B by RNA-interference differentially affects excitatory synapses and dendritic transport in rodent hippocampal neurons. Because of the embryonic lethality of KIF5B knockout mice that precludes their use to study the synaptic and cognitive functions of adult brain in vivo, we generate conditional knockout mice with specific depletion of KIF5B in excitatory neurons after birth. These KIF5B-deficient mice exhibit altered dendritic spine morphogenesis in the hippocampus, together with impaired hippocampal long-term potentiation and memory formation. Our findings reveal the unexpected functional specificity between two homologous motor proteins, and provide new insights into how expansion of the kinesin I family during evolution leads to diversification and specialization of motor proteins in neuron.		7月26日（金）9:45～10:00　第9会場（朱鷺メッセ　3F　306+307） 2O-09m2-2 海馬依存性の記憶はプラズマローゲンによって制御される Shamim Md Hossain（ホセインモハメドシャミン）¹，Yutaka Oomura（大村裕）¹，Takehiko Fujino（藤野武彦）²，Hiromitsu Tanaka（田中洋光）¹，Sanyu Sejimo（瀬下燦雄）¹ ¹九州大学医学研究院加齢病態修復学講座 ²レオロジー機能食品研究所 It has been reported that special phospholipids, plasmalogens (Pls), are reduced in brains of Alzheimer's disease (AD) patients. However, the role of these lipids in the memory processes was mostly elusive. To investigate the Pls function, we injected lentiviruses encoding sh-RNA against a Pls-synthesizing enzyme, glyceronephosphate O-acyltransferase (GNPAT) gene in murine hippocampus. We have observed a reduction of Gnpat expression in hippocampus which was associated with a significant disturbance of spatial memory. Interestingly, Pls reduction in murine brain reduced Bdnf expression and other memory related genes. In addition, the Pls reduction enhanced glial cells activation and increased the accumulation of amyloid beta proteins in the murine hippocampus, suggesting that reduction of Pls can accelerate AD like pathologies. Pls-containing diet for 6 weeks significantly increased Pls content in the hippocampus and enhanced spatial memory with increased expressions of phosphorylated (p-)Akt, p-CREB and BDNF, which were blocked by intrahippocampal injection of an Akt inhibitor. The Pls-diet enhanced hippocampal long-term potentiation, adult neurogenesis and dendritic spine density. It also increased CREB recruitments onto its putative binding sites of BDNF gene. Analysis of lipid raft domains in the hippocampal cell membranes showed that the lipid rafts were enriched with Pls and BDNF receptor, TrkB. Interestingly, hippocampal TrkB in the lipid raft was increased by Pls-diet, while it was decreased in GNPAT knock-down mice. The Pls-induced memory enhancement was mediated by BDNF-TrkB signaling since it was blocked by intrahippocampal injection of sh-BDNF/TrkB. Finally, Pls-drinking (0.15-0.18 mg/day) for 9 months in triple transgenic Alzheimer's disease (AD) model mice attenuated accumulation of β-amyloid protein in the hippocampus and improved spatial memory. These findings suggest that Pls in hippocampus play a significant role in memory function through the BDNF-TrkB signaling and reduction of Pls may trigger the memory loss like AD patients.

7月26日（金）10:00～10:15　第9会場（朱鷺メッセ　3F　306+307） 2O-09m2-3 神経機能を制御するドコサヘキサエン酸 (DHA)の新規作用機序の解明 Shinichiro Suzuki（鈴木慎一郎），Kento Karita（苅田憲人），Yuka Yamamoto（山本優香），Naoyuki Inagaki（稲垣直之），Michinori Toriyama（鳥山道則）奈良先端大バイオサイエンス神経形態形成 Neurons require several external cues for their functions in the developing brain. Recent works demonstrated that consumption of docosahexaenoic acid (DHA), one of the free fatty acids that can not be synthesized de novo, improves learning and memory in mammals. The reduction of DHA in developmental brain exhibited abnormal brain formation including microcephaly and hydrocephalus. In addition, in vitro study using cultured neurons showed that DHA stimulation enhanced neurite outgrowth and dendritic spine formation. These findings suggested that DHA is one of the essential nutrition for normal brain development and functions via neural circuit formation. However, the molecular mechanism of normal brain development mediated by DHA is not fully understood. To investigate the function of DHA in neuronal development, we first performed the RNA sequence using a next-generation sequencer to identify the up- or down-regulated genes induced by DHA in cultured mouse hippocampal neurons. Totally 21556 transcripts were detected in our assay, and 114 genes were up-regulated (> 1.5-folds), some of which were reported to be involved in axon outgrowth and dendritic spine formation, whereas 146 genes were down-regulated (< 2/3-folds). This result suggested that DHA modulates neuronal function by regulating gene expression. Ring Finger Protein 39 (RNF39) is one of the genes up-regulated upon DHA stimulation. To address the gene function of RNF39 for neuronal development, we performed overexpression and knockdown of RNF39. RNF39 overexpressing cells increased the number of dendritic spine, in contrast, knock down of RNF39 decreased the number of dendritic spine. These results suggested that RNF39 has a positive role for dendritic spine formation. Next, we performed immunoprecipitation of RNF39 and identified p53 and MDM2 as novel RNF39 interacting proteins. This result raises the possibility that RNF39 promotes dendritic spine formation by regulating p53 and MDM2 function.		7月26日（金）10:15～10:30　第9会場（朱鷺メッセ　3F　306+307） 2O-09m2-4 スパイン形成を制御するLMTK1-TBC1D9B-Rab11シグナル経路 Shin-ichi Hisanaga（久永眞市）¹，Taro Saito（斎藤太郎）¹，Tetsuya Takano（高野哲也）¹，Anni Huo（カクアンニ）¹，Koji Tsutsumi（堤弘次,）¹，Makoto Taniguchi（谷口誠）²，Kanae Ando（安藤香奈絵）¹，Mineko Tomomura（友村美根子）³，MItsunori Fukuda（福田光則）⁴，Hironori Nishino（西野尋紀）¹ ¹首都大学東京理生命科学 ²Dept Neurosci, Med Univ South Carolina, Charleston, USA ³明海大学歯 ⁴東北大学　生命科学 Dendritic spines are mushroom-like postsynaptic protrusions at excitatory synapses that are critical for proper neuronal synaptic transmission. While lipid and protein membrane components are necessary for spine formation, it is largely unknown how they are recruited to developing spines. Endosomal trafficking is one mechanism that may influence this development. We recently reported that Lemur kinase 1A (LMTK1A), a membrane-bound Ser/Thr kinase, regulates trafficking of endosomes in neurons. LMTK1 has been shown to be a p35 Cdk5 activator-binding protein and a substrate for Cdk5-p35, however, its neuronal function has not been sufficiently studied. Here, we investigate the role of LMTK1 in spine formation. Depletion of LMTK1 increases spine formation, maturation and density in primary cultured neurons and in mouse brain. Additionally, expression of kinase negative (kn) LMTK1 stimulates spine formation in primary neurons and in vivo. LMTK1 controls spine formation through Rab11, a regulator of recycling endosome trafficking. We identify the Rab11A GAP, TBC1D9B, as a LMTK1 binding protein, and find that TBC1D9B mediates LMTK1 activity on Rab11A. TBC1D9B inactivates Rab11A under the control of LMTK1A. Further, by analyzing the effect of decreased TBC1D9B expression in primary neurons, we demonstrate that TBC1D9B indeed regulates spine formation. This is the first demonstration of the biological function of TBC1D9B. Together, with the regulation of LMTK1 by Cdk5-p35, we propose the Cdk5-LMTK1-TBC1D9B-Rab11A cascade as a novel signaling mechanism regulating endosomal transport for synapse formation and function.