論文 - 柚崎　通介

Optogenetic Control of Synaptic AMPA Receptor Endocytosis Reveals Roles of LTD in Motor Learning

Kakegawa W., Katoh A., Narumi S., Miura E., Motohashi J., Takahashi A., Kohda K., Fukazawa Y., Yuzaki M., Matsuda S.

Neuron （Neuron）  99 （ 5 ） 985 - 998.e6 2018年09月

ISSN  08966273

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© 2018 Elsevier Inc. Long-term depression (LTD) of AMPA-type glutamate receptor (AMPA receptor)-mediated synaptic transmission has been proposed as a cellular substrate for learning and memory. Although activity-induced AMPA receptor endocytosis is believed to underlie LTD, it remains largely unclear whether LTD and AMPA receptor endocytosis at specific synapses are causally linked to learning and memory in vivo. Here we developed a new optogenetic tool, termed PhotonSABER, which enabled the temporal, spatial, and cell-type-specific control of AMPA receptor endocytosis at active synapses, while the basal synaptic properties and other forms of synaptic plasticity were unaffected. We found that fiberoptic illumination to Purkinje cells expressing PhotonSABER in vivo inhibited cerebellar motor learning during adaptation of the horizontal optokinetic response and vestibulo-ocular reflex, as well as synaptic AMPA receptor decrease in the flocculus. Our results demonstrate that LTD and AMPA receptor endocytosis at specific neuronal circuits were directly responsible for motor learning in vivo. Video Abstract: Kakegawa et al. show that AMPA receptor endocytosis at parallel fiber-Purkinje cell synapses in the cerebellar flocculus plays a direct role in motor learning in vivo, using a new optogenetic tool, PhotonSABER, which enables the acute inhibition of AMPA receptor endocytosis during LTD.

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Rab family small GTPases-mediated regulation of intracellular logistics in neural development

Shikanai M., Yuzaki M., Kawauchi T.

Histology and Histopathology （Histology and Histopathology）  33 （ 8 ） 765 - 771 2018年08月

ISSN  02133911

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© 2018, Histology and Histopathology. All rights reserved. Rab family small GTPases play essential roles in various cellular events via the regulation of intracellular logistics comprising a large number of membrane traffic pathways. Emerging evidence reveals the physiological roles of Rab proteins in several tissues, including developing brains. Many Rab proteins, such as Rab5, Rab6, Rab7, Rab8, Rab10, Rab11, Rab17 and Rab18, are shown to regulate neurite outgrowth in PC12 cells and/or axon and dendrite formation in primary cultured neurons. Recent studies have also revealed in vivo roles of several Rab family small GTPases in brain development and its related neurological disorders. In this review, we introduce the physiological function of Rab family proteins in neural development with particular focus on neurite outgrowth and neuronal migration.

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[Molecular Mechanisms for Learning and Memory: What Happens at the Synapses?].

Kakegawa W, Yuzaki M

Brain and nerve = Shinkei kenkyu no shinpo 70 （ 7 ） 677 - 687 2018年07月

ISSN  1881-6096

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Functional interactions between transient receptor potential M8 and transient receptor potential V1 in the trigeminal system: Relevance to migraine pathophysiology

Kayama Y., Shibata M., Takizawa T., Ibata K., Shimizu T., Ebine T., Toriumi H., Yuzaki M., Suzuki N.

Cephalalgia （Cephalalgia）  38 （ 5 ） 833 - 845 2018年04月

ISSN  03331024

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© 2017, © International Headache Society 2017. Background: Recent genome-wide association studies have identified transient receptor potential M8 (TRPM8) as a migraine susceptibility gene. TRPM8 is a nonselective cation channel that mediates cool perception. However, its precise role in migraine pathophysiology is elusive. Transient receptor potential V1 (TRPV1) is a nonselective cation channel activated by noxious heat. Both TRPM8 and TRPV1 are expressed in trigeminal ganglion (TG) neurons. Methods: We investigated the functional roles of TRPM8 and TRPV1 in a meningeal inflammation-based migraine model by measuring the effects of facial TRPM8 activation on thermal allodynia and assessing receptor coexpression changes in TG neurons. We performed retrograde tracer labeling to identify TG neurons innervating the face and dura. Results: We found that pharmacological TRPM8 activation reversed the meningeal inflammation-induced lowering of the facial heat pain threshold, an effect abolished by genetic ablation of TRPM8. No significant changes in the heat pain threshold were seen in sham-operated animals. Meningeal inflammation caused dynamic alterations in TRPM8/TRPV1 coexpression patterns in TG neurons, and colocalization was most pronounced when the ameliorating effect of TRPM8 activation on thermal allodynia was maximal. Our tracer assay disclosed the presence of dura-innervating TG neurons sending collaterals to the face. Approximately half of them were TRPV1-positive. We also demonstrated functional inhibition of TRPV1 by TRPM8 in a cell-based assay using c-Jun N-terminal kinase phosphorylation as a surrogate marker. Conclusions: Our findings provide a plausible mechanism to explain how facial TRPM8 activation can relieve migraine by suppressing TRPV1 activity. Facial TRPM8 appears to be a promising therapeutic target for migraine.

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Two Classes of Secreted Synaptic Organizers in the Central Nervous System

Yuzaki M.

Annual Review of Physiology （Annual Review of Physiology）  80   243 - 262 2018年02月

ISSN  00664278

　概要を見る

© 2018 by Annual Reviews. All rights reserved. Research in the last two decades has identified many synaptic organizers in the central nervous system that directly regulate the assembly of pre- and/or postsynaptic molecules, such as synaptic vesicles, active zone proteins, and neurotransmitter receptors. They are classified into secreted factors and cell adhesion molecules, such as neurexins and neuroligins. Certain secreted factors are termed extracellular scaffolding proteins (ESPs) because they are components of the synaptic extracellular matrix and serve as a scaffold at the synaptic cleft. These include Lgi1, Cbln1, neuronal pentraxins, Hevin, thrombospondins, and glypicans. Diffusible secreted factors, such as Wnts, fibroblast growth factors, and semaphorins, tend to act from a distance. In contrast, ESPs remain at the synaptic cleft and often help synaptic adhesion and/or accumulation of postsynaptic receptors. Many fundamental questions remain about when, how, and why various synaptic organizers establish and modify the vast numbers of connections during development and throughout life.

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Nav1.2 haplodeficiency in excitatory neurons causes absence-like seizures in mice.

Ogiwara I, Miyamoto H, Tatsukawa T, Yamagata T, Nakayama T, Atapour N, Miura E, Mazaki E, Ernst SJ, Cao D, Ohtani H, Itohara S, Yanagawa Y, Montal M, Yuzaki M, Inoue Y, Hensch TK, Noebels JL, Yamakawa K

Communications biology 1   96 2018年

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Signaling Pathways Relevant to Nerve Growth Factor-induced Upregulation of Transient Receptor Potential M8 Expression.

Kayama Y, Shibata M, Takizawa T, Ibata K, Nakahara J, Shimizu T, Toriumi H, Yuzaki M, Suzuki N

Neuroscience 367   178 - 188 2017年12月

ISSN  0306-4522

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Dendritic Homeostasis Disruption in a Novel Frontotemporal Dementia Mouse Model Expressing Cytoplasmic Fused in Sarcoma.

Shiihashi G, Ito D, Arai I, Kobayashi Y, Hayashi K, Otsuka S, Nakajima K, Yuzaki M, Itohara S, Suzuki N

EBioMedicine 24   102 - 115 2017年10月

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Neural differentiation of human embryonic stem cells induced by the transgene-mediated overexpression of single transcription factors.

Matsushita M, Nakatake Y, Arai I, Ibata K, Kohda K, Goparaju SK, Murakami M, Sakota M, Chikazawa-Nohtomi N, Ko SBH, Kanai T, Yuzaki M, Ko MSH

Biochemical and biophysical research communications 490 （ 2 ） 296 - 301 2017年08月

ISSN  0006-291X

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The C1q complement family of synaptic organizers: not just complementary.

Yuzaki M

Current opinion in neurobiology 45   9 - 15 2017年08月

ISSN  0959-4388

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Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells.

Miyazaki T, Yamasaki M, Hashimoto K, Kohda K, Yuzaki M, Shimamoto K, Tanaka K, Kano M, Watanabe M

Proceedings of the National Academy of Sciences of the United States of America 114 （ 28 ） 7438 - 7443 2017年07月

ISSN  0027-8424

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MTCL1 plays an essential role in maintaining Purkinje neuron axon initial segment.

柚﨑 通介

The EMBO journal 36 （ 9 ） 1227 - 1242 2017年05月

研究論文（学術雑誌）,  ISSN  0261-4189

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Chemical labelling for visualizing native AMPA receptors in live neurons.

柚﨑 通介

Nature communications 8   138 - 150 2017年04月

研究論文（学術雑誌）,  ISSN  2041-1723

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A GluD Coming-Of-Age Story.

柚﨑 通介

Trends in neurosciences 40 （ 3 ） 138 - 150 2017年03月

研究論文（学術雑誌）,  ISSN  0166-2236

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Rapid differentiation of human pluripotent stem cells into functional neurons by mRNAs encoding transcription factors.

柚﨑 通介

Scientific reports 7   25577 - 25587 2017年02月

研究論文（学術雑誌）,  ISSN  2045-2322

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Roles of Cbln1 in Non-Motor Functions of Mice.

Otsuka S, Konno K, Abe M, Motohashi J, Kohda K, Sakimura K, Watanabe M, Yuzaki M

The Journal of neuroscience : the official journal of the Society for Neuroscience 36 （ 46 ） 11801 - 11816 2016年11月

ISSN  0270-6474

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Involvement of GluD2 in Fear-Conditioned Bradycardia in Mice.

柚﨑 通介

PloS one 11 （ 11 ） 958 - 967 2016年11月

研究論文（学術雑誌）,  ISSN  1932-6203

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Allosteric activation of membrane-bound glutamate receptors using coordination chemistry within living cells.

柚﨑 通介

Nature chemistry 8 （ 10 ） 958 - 967 2016年10月

研究論文（学術雑誌）,  ISSN  1755-4330

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Structural basis for integration of GluD receptors within synaptic organizer complexes.

Elegheert J, Kakegawa W, Clay JE, Shanks NF, Behiels E, Matsuda K, Kohda K, Miura E, Rossmann M, Mitakidis N, Motohashi J, Chang VT, Siebold C, Greger IH, Nakagawa T, Yuzaki M, Aricescu AR

Science (New York, N.Y.) 353 （ 6296 ） 295 - 9 2016年07月

ISSN  0036-8075

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Transsynaptic Modulation of Kainate Receptor Functions by C1q-like Proteins.

Matsuda K, Budisantoso T, Mitakidis N, Sugaya Y, Miura E, Kakegawa W, Yamasaki M, Konno K, Uchigashima M, Abe M, Watanabe I, Kano M, Watanabe M, Sakimura K, Aricescu AR, Yuzaki M

Neuron 90 （ 4 ） 752 - 67 2016年05月

ISSN  0896-6273

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