Welcome to Yuzaki Lab
    Yuzaki Lab's (Department of Neurophysiology, Keio University School of Medicine) research theme is to elucidate "how neural activity and environmental changes induce memory and learning,、, 、and how they change the neural network itself ."。For details please Click here.
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We await the participation of motivated indivisuals。We will vigorously nurture young researchers who will lead the future of basic science.。
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■LGI1 is、Secreted from axons in response to neural activity and suppresses glutamate release (Cell Reports) 2024.5.28 Cuhadar U, Footwear-Reyes L, Pascual-Caro C, Aberra AS, Ritzau-Jost A, Aggarwal A, Ibata K, Podgorski K, Yuzaki M, Geiss C, Hallerman S, Jump MB, by Juan-Sanz J. Activity-driven synaptic translocation of LGI1 controls excitatory neurotransmission. Cell Rep. 43:114186, 2024..
LGI1 is a synaptogenic molecule belonging to extracellular scaffold proteins。LGI1 is secreted in response to neural activity and promotes synapse formation.、Found to suppress glutamate release。Interestingly, Cbln1 is tetanus toxin (TeNT)(VAMP1-3 independent)、We previously reported that it is secreted by Syntaxin-4 and SNAP49-dependent SNAREs.。In contrast, LGI1 secretion was partially inhibited by TeNT.、Because it does not depend on SNAP29、found to be released by separate SNARE complexes。In this paper, Yuzaki Lab conducted joint research on analysis technology for SNARE complexes.。

■CPTX is、Promoting synapse formation on iPS transplanted cells in spinal cord injury model mice (Stem Cell Reports) 2024.2.3 Saijo Y, Nagoshi N, Kawai M, Kitagawa T, Suematsu Y, Ozaki M, Shinozaki M, Kohyama J, Shibata S, Takeuchi K, Nakamura M, Yuzaki M, Okano H. Human-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury. Stem Cell Reports S2213-6711(24)00010-9, 2024..
Transplantation of neural stem/progenitor cells (NS/PC) derived from human induced pluripotent stem cells (hiPSC)、Shows promise in animal models of spinal cord injury (SCI)。For recovery of motor function、It is important to establish functional synaptic connections between transplanted neurons and host neurons。In this paper,、We have developed ex vivo gene therapy in which the artificial synaptic connector CPTX developed by Yuzaki Lab is expressed in hiPSC-NS/PCs in advance and then transplanted.。Using immunodeficient transgenic SCI model rats、Where histological and functional analysis was performed、It was revealed that the formation of excitatory synapses at the transplantation site of CPTX-expressing hiPSC-NS/PCs was significantly increased.。Also、Tracking of retrograde monosynapses、CPTX has been shown to cause extensive integration of transplanted neurons into surrounding neural tracts.、Motor function and spinal conduction also improved.。This study、Orthopedic surgeon Saijo-san、This is a joint research with Okano Lab.。

■DSCAM is、Controls the perisynaptic localization of GLAST in Bergmann glia and participates in synapse formation(Nature Commun)2024.2.3 Dewa KI, Arimu N, Kakegawa W, Itoh M, Adachi T, Miyashita S, Inoue YU, Hizawa K, Hori K, Honjoya N, Yagishita H, Taya S, Miyazaki T, Usui C, Tatsumoto S, Tsuzuki A, Uetake H, Sakai K, Yamakawa K, Sasaki T, Nagai J, Kawaguchi Y, Sone M, Inoue T, Go Y, Ichinohe N, Kaibuchi K, Watanabe M, Koizumi S, Yuzaki M, Hoshino M. Neuronal DSCAM regulates the peri-synaptic localization of GLAST in Bergmann glia for functional synapse formation. Nat Commun. 15:458, 2024..

in the central nervous system、Astrocytes clear glutamate from the synaptic cleft.、Achieves proper synaptic function。However、How does the astrocytic glutamate transporter GLAST function around synapses?、it was still unclear。In this paper、Cell adhesion molecule (DSCAM) expressed in Purkinje cells、By controlling the localization of GLAST expressed in Bergmann glia、Climbing fibers were shown to be involved in Purkinje cell synapse formation and cerebellar motor learning.。This is a huge amount of work done by Mr. Dewa of Hoshino Lab.。For the Yuzaki lab, Kakegawa was in charge of electrophysiological analysis and eye movement learning test.。

■Bioorthogonal chemical labeling of endogenous neurotransmitter receptors in the living mouse brain(PNAS)2024.1.31 Nonaka H, Sakamoto S, Shiraiwa K, Ishikawa M, Tamura T, Okuno K, Kondo T, Kiyonaka S, Susaki EA, Shimizu C, Ueda HR, Kakegawa W, Arai I, Yuzaki M, Hamachi I. Bioorthogonal chemical labeling of endogenous neurotransmitter receptors in living mouse brains. Proc Natl Acad Sci USA. 121:e2313887121, 2024..

How to covalently chemically label proteins without genetic manipulation、is a powerful method for analyzing receptors。However、Selective target receptor labeling in the brain has not yet been established。In this research led by Mr. Nonaka of Kyoto University's Hamachi Laboratory,、using ligand-directed chemical reactions、We show that synthetic probes can selectively bind to target endogenous receptors in the brain of living mice.。Kakegawa of Yuzaki Lab、As part of the joint research between CREST and ERATO, Arai、In this study, we showed that chemical labeling does not change receptor function.。

■Another hidden face of GluD1 in inhibitory synapses(Cell Research)2024.1.24 Masayuki Itoh, Michisuke Yuzaki. The hidden face of GluD1 at inhibitory synapses. Cell Res. 2024 Jan 23.

The δ-type glutamate receptors (GluD1 and GluD2) belong to the ionotropic glutamate receptors.、It has long been called an orphan receptor because it does not bind glutamate.。GluD2 isexcitatory synapseIn、① Binds to Cbln1 released from the presynapse to control synapse formation and maintenance、② Binds to D-Ser released by glia and induces synaptic plasticity LTD、It was found that the function of。Interestingly、GluD1 isinhibitory synapseIn、① Binds with Cbln4 released from the presynapse to control synapse formation and maintenance。However, it was unclear whether GluD1 controls synaptic plasticity.。Nozawa-kun, together with Hayashi-san、By Piot et al.、GluD1 is、②Showed to bind to GABA and control LTP at inhibitory synapses。In this review、We introduce this paper and summarize the remaining issues.。