■ Development process of dendrites and their molecular mechanism-using Pulkinje cells as a model（Cerebellum as a CNS Hub）2021.11.11

Takeo Y.H., Yuzaki M. (2021) Purkinje Cell Dendrites: The Time-Tested Icon in Histology. In: Mizusawa H., Kakei S. (eds) Cerebellum as a CNS Hub. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-030-75817-2_7.

By developing unique dendrites in each nerve cell、Form the proper neural circuit。However, the molecular mechanism by which dendrites are formed is not fully understood.。Because cerebellar Purkinje cells develop highly developed dendrites after birth、It has been used as an optimal model for the study of dendrite development mechanism.。In this review、Mr. Takeo summarizes past research along with his own research results、Discussing the direction of future research。

■ Elucidation of AMPA receptor subunit-specific endocytosis mechanism（J Biol Chem）2021.7.24

Matsuda S, Yuzaki M. Subunit-dependent and independent rules of AMPA receptor trafficking during chemical long-term depression in hippocampal neurons.J Biol Chem 297(2), 2021. doi:10.1016/j.jbc.2021.100949.

Long-term repression phenomenon (LTD), which is considered to be the basic course of memory and learning)Is the number of AMPA receptors in the postsynaptic、It is believed that its molecular level entity is reduced due to internalization (endocytosis) by neural activity.。By phosphorylating the intracellular domain, which is conventionally different for each subunit of AMPA receptor、It was thought that the endocytosis of the AMPA receptor itself was regulated。On the other hand、Phosphorylation of TARP that binds to AMPA receptor regardless of AMPA receptor subunit、From binding AP-2, which is essential for endocytosis, to the AMPA-TARP complex、It was a mystery how AMPA receptor subunits could control LTD.。In this paper、The phosphorylation status of the GluA1 subunit of the AMPA receptor、Discovered to change the strength of the bond between TARP and AP-2。Although TARP cannot distinguish the subunits of AMPA receptors、AP-2 can distinguish the phosphorylation state of each subunit of AMPA-TARP receptor.。
This is the result of the work of Mr. Matsuda (currently an associate professor at the University of Electro-Communications) who has continued since he was enrolled in this classroom.。Congratulations!。

■ For the special issue in memory of Professor Masao Ito（Neuroscience）2021.5.10

Nagao S, Hirai H, Kano M, Yuzaki M. Masao Ito-A Visionary Neuroscientist with a Passion for the Cerebellum. Neuroscience 462:1-3, 2021. Neuroscience. 2021. 5. 10. doi: 10.1016/j.neuroscience.2021.02.028. PMID: 33892899

Leading the world in cerebral neural circuit research as a learning machine、And edited a special issue in memory of Dr. Masao Ito, who contributed to the development of Japanese neuroscience.。While praying for souls、I would like to promote research so as not to extinguish the fire。

■ Autism-related protein CHD8 is essential for cerebellar development and motor function（Cell Rep）2021.4.6

Kawamura A, Katayama Y, Kakegawa W, Ino D, Nishiyama M, Yuzaki M, Nakayama KI. The autism-associated protein CHD8 is required for cerebellar development and motor function. Cell Rep. 2021. 4. 6. DOI: 10.1016/j.celrep.2021.108932

The chromatin-modified gene, CHD8, is known as one of the genes most associated with the development of autism spectrum disorders.。On the other hand、Although abnormalities in the cerebellum have long been reported in patients with autism spectrum disorders、The association between CHD8 and the cerebellar phenotype was unknown。In this study, by knocking out the CHD8 gene specifically for cerebellar granule cells、Clarified the role of the CHD8 gene in cerebellar development and motor function。This is a joint research with Kyushu University Nakayama Lab.。Associate Professor Kakegawa was in charge of electrophysiological phenotypic analysis of the cerebellum。

■ Breaking the old and creating the new-activity-dependent lysosome secretion in nerve cells（Neurosci Res）2021.4.15

Ibata K, Yuzaki M. Destroy the old to build the new: Activity-dependent lysosomal exocytosis in neurons. Neurosci Res. 2021 in press. doi.org/10.1016/j.neures.2021.03.011.

Even in everyday life、Even in nature world、When making something new、Oftentimes, you must break the old one before that。When the morphology of nerve cells changes in our brain according to the developmental stage and memory / learning、Cooperately、It is always accompanied by the destruction of nerve cells and the extracellular matrix around them。As one of the mechanisms responsible for such scrap and build phenomenon、The secretion of lysosomes from nerve cells is raising attention。Although lysosomes are usually known as the final digestion site for aging intracellular products,、,、We have found that, In response to hyperactivity, it releases the synapse-forming molecule Cbln1 with the lysosome enzyme, which is the content of the lysosome (Neuron 2019).。In this review the、we overviewed lysosome secretion in the nervous system。Dr. Ibata, who has transferred to St. Marianna University, is the first author.。

■ Quantification of glutamate receptor transport process using ligand-directed two-step labeling method（Common Nat）2021.2.5

Ojima K, Shiraiwa K, Soga K, Doura T, Takato M, Komatsu K, Yuzaki M, Hamachi I, Kiyonaka S. Ligand-directed two-step labeling to quantify neuronal glutamate receptor trafficking. Nat Commun. 2021 Feb 5;12(1):831. doi: 10.1038/s41467-021-21082-x.

Excitatory neurotransmitter in our brain are borne by glutamate、Especially AMPA receptor is an important receptor that convey the fast neurotransmission。It is what the number of AMPA receptors in the postsynaptic changes in the long term、It is thought that the most fundamental processes of memory。To visualize and quantify the transport process of this receptor、2017Developed a new chemical labeling method in the year。This paper further improves this labeling method.、Labeling in a shorter time is now possible。It also shows how to label NMDA receptors.。This research was conducted by the Nagoya University Kiyochu Lab.、This is the result of joint research with Kyoto University Hamaji Lab.。

■ Development and usefulness of new epitope tagsBioorg Med Chem2021.1.15

Thimaradka v, Hoon Oh J, Heroven C, Radu Aricescu A, Yuzaki M, Tamura T, Hamachi I.  Site-specific covalent labeling of His-tag fused proteins with N-acyl-N-alkyl sulfonamide reagent. Bioorg Med Chem 2021 Jan 15;30:115947. doi: 10.1016/j.bmc.2020.115947.

To a specific part of the protein、Technology for introducing amino acid residues with new functions、Important in various fields。For this、First, the epitope tag is introduced at a specific site of the protein.。This epitope tag is、As much as possible without impairing the function of the original protein、And it needs to be specifically chemically modified。In this paper, it consists of histidine (H) and lysine (K).、Showed the usefulness of short epitope tags KH6 and H6K。This research is the result of joint research with Kyoto University Hamaji Lab.。