The role of the trafficking of PlexinA4-containing vesicles in dendritic development

• Project/Area Number: 24500444
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Yokohama City University
• Principal Investigator: YAMASHITA Naoya 横浜市立大学, 医学(系)研究科(研究院), 客員講師 (40508793)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: セマフォリン / プレキシン / グルタミン酸受容体 / 樹状突起成熟

Outline of Final Research Achievements

Neurons are highly polarized cells with axon, dendrites, and cell body. These subcellular compartments need to communicate with each other. For example, signals received in distal axon travel long distances to reach the cell body and/or dendrites. In present study, I identified that the signal elicited by semaphorin3A (Sema3A), a repulsive axon guidance molecule, enhances dendritic transport of glutamate receptors in hippocampal neurons through PlexinA4, one of the receptor component of Sema3A. I further found that this novel Sema3A action that enhances glutamate receptor trafficking is also required for dendritic morphology and maturation. My findings therefore play an essential role in proper neuronal development.

Research Products

• [Journal Article] Anti-Semaphorin 3A neutralization monoclonal antibody prevents sepsis development in lipopolysaccharide-treated mice (2015)
  • Author(s): Naoya Yamashita, Aoi Jitsuki-Takahashi, Miyuki Ogawara, Wataru Ohkubo, Tomomi Araki, Chie Hotta, Tomohiko Tamura, Shu-ichi Hashimoto, Takashi Yabuki, Toru Tsuji, Yukie Sasakura, Hiromi Okumura, Aki Takaiwa, Chika Koyama, Koji Murakami and Yoshio Goshima
  • Journal Title: International immunology Volume: 印刷中 Issue: 9 Pages: 1-8
  • DOI: 10.1093/intimm/dxv014
  • Peer Reviewed
• [Journal Article] Semaphorin3A-induced axonal transport mediated through phosphorylation of Axin-1 by GSK3β. (2014)
  • Author(s): Hida T, Nakamura F, Usui H, Takeuchi K, Yamashita N, Goshima Y.
  • Journal Title: Brain Research Volume: 1598 Pages: 46-56
  • DOI: 10.1016/j.brainres.2014.12.028
  • Peer Reviewed
• [Journal Article] lexinA4-dependent retrograde Semaphorin3A signaling regulates the dendritic localization of GluA2-containing AMPA receptors. (2014)
  • Author(s): 1) Yamashita, N., Usui, H., Nakamura, F., Chen, S., Sasaki, Y., Hida, T., Suto, F., Taniguchi, M., Takei, K., Goshima, Y.
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 3424-3424
  • DOI: 10.1038/ncomms4424
  • Peer Reviewed / Open Access
• [Journal Article] Mice lacking collapsin response mediator protein 1 manifest hyperactivity, impaired leaming and memory, and impaired prepulse inhibition (2013)
  • Author(s): Yamashita N, Takahashi A, Takao K, Yamamoto T, Kolattukudy P, Miyakawa T, Goshima Y
  • Journal Title: Frontiers in Behavioral Neuroscience Volume: 7巻 Pages: 216-226
  • DOI: 10.3389/fnbeh.2013.00216
  • Peer Reviewed / Open Access
• [Journal Article] Amyloid-β25–35 induces impairment of cognitive function andlong-term potentiation through phosphorylation of collapsinresponse mediator protein 2. (2013)
  • Author(s): Isono T, Yamashita N, Obara M, Araki T, Nakamura F, Kamiya Y, Alkam T, Nitta A, Nabeshima T, Mikoshiba K, Ohshima T, Goshima Y
  • Journal Title: Neurosci Res Volume: 77 Issue: 3 Pages: 180-185
  • DOI: 10.1016/j.neures.2013.08.005
  • Peer Reviewed
• [Journal Article] Collapsin response mediator protein 4 affects the number of tyrosine hydroxylase-immunoreactive neurons in the sexually dimorphic nucleus in female mice. (2013)
  • Author(s): Iwakura T, Sakoh M, Tsutiya A, Yamashita N, Ohtani A, Tsuda M, Ogawa S, Tsukahara S, Nishihara M, Shiga T, Goshima Y, Kato T, Ohtani-Kaneko R.
  • Journal Title: Dev Neurobiol. Volume: 237 Issue: 7 Pages: 502-517
  • DOI: 10.1002/dneu.22076
  • Peer Reviewed
• [Journal Article] Class 3 semaphorins as a therapeutic target (2012)
  • Author(s): Goshima Y., Sasaki Y., Yamashita N., Nakamura F
  • Journal Title: Expert Opin.Ther. Targets Volume: 16 Issue: 9 Pages: 933-944
  • DOI: 10.1517/14728222.2012.710201
  • Peer Reviewed
• [Journal Article] GSK3β/Axin-1/β-Catenin Complex Is Involved in Semaphorin3A Signaling. (2012)
  • Author(s): Hida T, Yamashita N, Usui H, Nakamura F, Sasaki Y, Kikuchi A, Goshima Y
  • Journal Title: The Journal of neuroscience Volume: 32 Pages: 11905-11918
  • Peer Reviewed
• [Journal Article] Phosphorylation of CRMP2 is involved in proper bifurcation of the apical dendrite of hippocampal CA1 pyramidal neurons. (2012)
  • Author(s): Niisato E, Nagai1 J, Yamashita N, Nakamura F, Goshima Y, Ohshima T
  • Journal Title: Developmental neurobiology Volume: 73 Issue: 2 Pages: 142-151
  • DOI: 10.1002/dneu.22048
  • Peer Reviewed
• [Journal Article] Semaphorin3A facilitates axonal transport through a local calcium signaling and tetrodotoxin-sensitive voltage-gated sodium channels (2012)
  • Author(s): Yamane M, Yamashita N, Yamamoto H, Iizuka A, Shouji M, Usui H, Goshima Y.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 422(2) Issue: 2 Pages: 333-38
  • DOI: 10.1016/j.bbrc.2012.05.003
  • Peer Reviewed
• [Journal Article] Collapsin Response Mediator Proteins Regulate Neuronal Development and Plasticity by Switching Their Phosphorylation Status (2012)
  • Author(s): Yamashita N, Goshima Y.
  • Journal Title: Molecular Neurobiology Volume: 45(2) Issue: 2 Pages: 234-46
  • DOI: 10.1007/s12035-012-8242-4
  • Peer Reviewed
• [Journal Article] Phosphorylation of CRMP2 (collapsin response mediator protein 2) is involved in proper dendritic field organization. (2012)
  • Author(s): Yamashita N, Ohshima T, Nakamura F, Kolattukudy P, Honnorat J, Mikoshiba K, Goshima Y
  • Journal Title: The Journal of neuroscience Volume: 32 Pages: 1360-1365
  • Peer Reviewed
• [Presentation] A retrograde axonal transport elicited by Semaphorin3A regulates dendritic arborization through localization of AMPA receptor subunit GluA2 in dendrites (2013)
  • Author(s): 山下直也、五嶋良郎
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] Keystone symposia “Cell Biology and Pathology of Axons”. (2013)
  • Author(s): Yamashita N, Goshima Y
  • Organizer: A Retrograde axonal transport elicited by Semaphorin3A Drives AMPA Receptor Subunit GluA2 to Dendrites.
  • Place of Presentation: Tahoe Citｙ, USA
• [Presentation] A retrograde axonal transport elicited by Semaphorin3A drives AMPA receptor subunit GluA2 to dendrites. (2013)
  • Author(s): 山下直也、五嶋良郎
  • Organizer: 日本生理学会大会
  • Place of Presentation: タワーホール船堀（東京都）
  • Invited
• [Presentation] Cold Spring Harbor Laboratory meeting “Axon Guidance, Synapse Formation and Regeneration” (2012)
  • Author(s): Yamashita N, Chen S, Goshima Y
  • Organizer: Semaphorin3A drives AMPA Receptor Subunit GluA2 to dendrites by a retrograde signaling via axonal transport.
  • Place of Presentation: New York, USA
• [Remarks] 横浜市立大学分子薬理神経生物学
  • URL: http://www-user.yokohama-cu.ac.jp/~pharmac/
• [Remarks] http://www-user.yokohama-cu.ac.jp/~pharmac/
• [Remarks] 横浜市立大学分子薬理神経生物学
  • URL: http://www-user.yokohama-cu.ac.jp/~pharmac/