研究者総覧

三木 玄方 (ミキ ハルカタ)

  • 解剖学講座(解剖学部門) 講師
メールアドレス: hmikijichi.ac.jp
Last Updated :2021/09/22

研究者情報

学位

  • 医学博士(東京大学)

ホームページURL

J-Global ID

研究キーワード

  • 微小管   キネシン   細胞内輸送   分子モーター   

研究分野

  • ライフサイエンス / 解剖学 / 細胞生物学

経歴

  • 2012年09月 - 現在  自治医科大学解剖学部門講師
  • 2003年04月 - 2012年08月  東京大学大学院・医学(系)研究科助教

学歴

  • 1997年04月 - 2001年03月   東京大学大学院   医学系研究科   分子再某生物学専攻

研究活動情報

論文

  • Shinsuke Niwa, Kazuo Nakajima, Harukata Miki, Yusuke Minato, Doudou Wang, Nobutaka Hirokawa
    DEVELOPMENTAL CELL 23 6 1167 - 1175 2012年12月 [査読有り][通常論文]
     
    Cilia control homeostasis of the mammalian body by generating fluid flow. It has long been assumed that ciliary length-control mechanisms are essential for proper flow generation, because fluid flow generation is a function of ciliary length. However, the molecular mechanisms of ciliary length control in mammals remain elusive. Here, we suggest that KIF19A, a member of the kinesin superfamily, regulates ciliary length by depolymerizing microtubules at the tips of cilia. Kif19a(-/-) mice displayed hydrocephalus and female infertility phenotypes due to abnormally elongated cilia that cannot generate proper fluid flow. KIF19A localized to cilia tips, and recombinant KIF19A controlled the length of microtubules polymerized from axonemes in vitro. KIF19A had ATP-dependent microtubule-depolymerizing activity mainly at the plus end of microtubules. Our results indicated a molecular mechanism of ciliary length regulation in mammals, which plays an important role in the maintenance of the mammalian body.
  • H Miki, Y Okada, N Hirokawa
    TRENDS IN CELL BIOLOGY 15 9 467 - 476 2005年09月 [査読無し][通常論文]
     
    Kinesin superfamily proteins (KIFs) are key players or 'hub' proteins in the intracellular transport system, which is essential for cellular function and morphology. The KIF superfamily is also the first large protein family in mammals whose constituents have been completely identified and confirmed both in silico and in vivo. Numerous studies have revealed the structures and functions of individual family members; however, the relationships between members or a perspective of the whole superfamily structure until recently remained elusive. Here, we present a comprehensive summary based on a large, systematic phylogenetic analysis of the kinesin superfamily. All available sequences in public databases, including genomic information from all model organisms, were analyzed to yield the most complete phylogenetic kinesin tree thus far, comprising 14 families. This comprehensive classification builds on the recently proposed standardized nomenclature for kinesins and allows systematic analysis of the structural and functional relationships within the kinesin superfamily.
  • P Carninci, T Kasukawa, S Katayama, J Gough, MC Frith, N Maeda, R Oyama, T Ravasi, B Lenhard, C Wells, R Kodzius, K Shimokawa, VB Bajic, SE Brenner, S Batalov, ARR Forrest, M Zavolan, MJ Davis, LG Wilming, Aidinis, V, JE Allen, Ambesi-Impiombato, X, R Apweiler, RN Aturaliya, TL Bailey, M Bansal, L Baxter, KW Beisel, T Bersano, H Bono, AM Chalk, KP Chiu, Choudhary, V, A Christoffels, DR Clutterbuck, ML Crowe, E Dalla, BP Dalrymple, B de Bono, G Della Gatta, D di Bernardo, T Down, P Engstrom, M Fagiolini, G Faulkner, CF Fletcher, T Fukushima, M Furuno, S Futaki, M Gariboldi, P Georgii-Hemming, TR Gingeras, T Gojobori, RE Green, S Gustincich, M Harbers, Y Hayashi, TK Hensch, N Hirokawa, D Hill, L Huminiecki, M Iacono, K Ikeo, A Iwama, T Ishikawa, M Jakt, A Kanapin, M Katoh, Y Kawasawa, J Kelso, H Kitamura, H Kitano, G Kollias, SPT Krishnan, A Kruger, SK Kummerfeld, Kurochkin, IV, LF Lareau, D Lazarevic, L Lipovich, J Liu, S Liuni, S McWilliam, MM Babu, M Madera, L Marchionni, H Matsuda, S Matsuzawa, H Miki, F Mignone, S Miyake, K Morris, S Mottagui-Tabar, N Mulder, N Nakano, H Nakauchi, P Ng, R Nilsson, S Nishiguchi, S Nishikawa, F Nori, O Ohara, Y Okazaki, Orlando, V, KC Pang, WJ Pavan, G Pavesi, G Pesole, N Petrovsky, S Piazza, J Reed, JF Reid, BZ Ring, M Ringwald, B Rost, Y Ruan, SL Salzberg, A Sandelin, C Schneider, C Schonbach, K Sekiguchi, CAM Semple, S Seno, L Sessa, Y Sheng, Y Shibata, H Shimada, K Shimada, D Silva, B Sinclair, S Sperling, E Stupka, K Sugiura, R Sultana, Y Takenaka, K Taki, K Tammoja, SL Tan, S Tang, MS Taylor, J Tegner, SA Teichmann, HR Ueda, E van Nimwegen, R Verardo, CL Wei, K Yagi, H Yamanishi, E Zabarovsky, S Zhu, A Zimmer, W Hide, C Bult, SM Grimmond, RD Teasdale, ET Liu, Brusic, V, J Quackenbush, C Wahlestedt, JS Mattick, DA Hume, C Kai, D Sasaki, Y Tomaru, S Fukuda, M Kanamori-Katayama, M Suzuki, J Aoki, T Arakawa, J Iida, K Imamura, M Itoh, T Kato, H Kawaji, N Kawagashira, T Kawashima, M Kojima, S Kondo, H Konno, K Nakano, N Ninomiya, T Nishio, M Okada, C Plessy, K Shibata, T Shiraki, S Suzuki, M Tagami, K Waki, A Watahiki, Y Okamura-Oho, H Suzuki, J Kawai, Y Hayashizaki
    SCIENCE 309 5740 1559 - 1563 2005年09月 [査読有り][通常論文]
     
    This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
  • CJ Lawrence, RK Dawe, KR Christie, DW Cleveland, SC Dawson, SA Endow, LSB Goldstein, HV Goodson, N Hirokawa, J Howard, RL Malmberg, McIntosh, JR, H Miki, TJ Mitchison, Y Okada, ASN Reddy, WM Saxton, M Schliwa, JM Scholey, RD Vale, CE Walczak, L Wordeman
    JOURNAL OF CELL BIOLOGY 167 1 19 - 22 2004年10月 [査読有り][通常論文]
     
    In recent years the kinesin superfarnily has become so large that several different naming schemes have emerged, leading to confusion and miscommunication. Here, we set forth a standardized kinesin nomenclature based on 14 family designations. The scheme unifies all previous phylogenies and nomenclature proposals, while allowing individual sequence names to remain the same, and for expansion to occur as new sequences are discovered.
  • H Miki, M Setou, N Hirokawa
    GENOME RESEARCH 13 6B 1455 - 1465 2003年06月 [査読有り][通常論文]
     
    In the post genomic era where virtually all the genes and the proteins are known, an important task is to provide a comprehensive analysis of the expression of important classes of genes, such as those that are required for intracellular transport. We report the comprehensive analysis of the Kinesin Superfamily, which is the first and only large protein family whose constituents have been completely identified and confirmed in silico and at the cDNA, mRNA level. In FANTOM2, we have found 90 clones from 33 Kinesin Superfamily Protein (KIF) gene loci. The clones were analyzed in reference to sequence state, library of origin, detection methods, and alternative splicing. More than half of the representative transcriptional units (TU) were full length. The FANTOM2 library also contains novel splice variants previously unreported. We have compared and evaluated various protein classification tools and protein search methods using this data set. This report provides a foundation for future research of the intracellular transport along microtubules and proves the significance of intracellular transport protein transcripts as part of the transcriptome.
  • S Gustincich, S Batalov, KW Beisel, H Bono, P Carninci, CF Fletcher, S Grimmond, N Hirokawa, ED Jarvis, T Jegla, Y Kawasawa, J LeMieux, H Miki, E Raviola, RD Teasdale, N Tominaga, K Yagi, A Zimmer, Y Hayashizaki, Y Okazaki
    GENOME RESEARCH 13 6B 1395 - 1401 2003年06月 [査読有り][通常論文]
     
    We analyzed the mouse Representative Transcript and Protein Set for molecules involved in brain function. We found full-length cDNAs of many known brain genes and discovered new members of known brain gene families, including Family 3 G-protein coupled receptors, voltage-gated channels, and connexins. We also identified previously unknown candidates for secreted neuroactive molecules. The existence of a large number of unique brain ESTs suggests an additional molecular complexity that remains to be explored. A list of genes containing CAG stretches in the coding region represents a first step in the potential identification of candidates for hereditary neurological disorders.
  • Y Okazaki, M Furuno, T Kasukawa, J Adachi, H Bono, S Kondo, Nikaido, I, N Osato, R Saito, H Suzuki, Yamanaka, I, H Kiyosawa, K Yagi, Y Tomaru, Y Hasegawa, A Nogami, C Schonbach, T Gojobori, R Baldarelli, DP Hill, C Bult, DA Hume, J Quackenbush, LM Schriml, A Kanapin, H Matsuda, S Batalov, KW Beisel, JA Blake, D Bradt, Brusic, V, C Chothia, LE Corbani, S Cousins, E Dalla, TA Dragani, CF Fletcher, A Forrest, KS Frazer, T Gaasterland, M Gariboldi, C Gissi, A Godzik, J Gough, S Grimmond, S Gustincich, N Hirokawa, IJ Jackson, ED Jarvis, A Kanai, H Kawaji, Y Kawasawa, RM Kedzierski, BL King, A Konagaya, Kurochkin, IV, Y Lee, B Lenhard, PA Lyons, DR Maglott, L Maltais, L Marchionni, L McKenzie, H Miki, T Nagashima, K Numata, T Okido, WJ Pavan, G Pertea, G Pesole, N Petrovsky, R Pillai, JU Pontius, D Qi, S Ramachandran, T Ravasi, JC Reed, DJ Reed, J Reid, BZ Ring, M Ringwald, A Sandelin, C Schneider, CAM Semple, M Setou, K Shimada, R Sultana, Y Takenaka, MS Taylor, RD Teasdale, M Tomita, R Verardo, L Wagner, C Wahlestedt, Y Wang, Y Watanabe, C Wells, LG Wilming, A Wynshaw-Boris, M Yanagisawa, Yang, I, L Yang, Z Yuan, M Zavolan, Y Zhu, A Zimmer, P Carninci, N Hayatsu, T Hirozane-Kishikawa, H Konno, M Nakamura, N Sakazume, K Sato, T Shiraki, K Waki, J Kawai, K Aizawa, T Arakawa, S Fukuda, A Hara, W Hashizume, K Imotani, Y Ishii, M Itoh, Kagawa, I, A Miyazaki, K Sakai, D Sasaki, K Shibata, A Shinagawa, A Yasunishi, M Yoshino, R Waterston, ES Lander, J Rogers, E Birney, Y Hayashizaki
    NATURE 420 6915 563 - 573 2002年12月 [査読有り][通常論文]
     
    Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.
  • H Miki, M Setou, K Kaneshiro, N Hirokawa
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 98 13 7004 - 7011 2001年06月 [査読無し][招待有り]
     
    Intracellular transport is essential for morphogenesis and functioning of the cell. The kinesin superfamily proteins (KIFs) have been shown to transport membranous organelles and protein complexes in a microtubule- and ATP-dependent manner. More than 30 KIFs have been reported in mice. However, the nomenclature of KIFs has not been clearly established, resulting in various designations and redundant names for a single KIF. Here, we report the identification and classification of all KIFs in mouse and human genome transcripts. Previously unidentified murine KIFs were found by a PCR-based search. The identification of all KIFs was confirmed by a database search of the total human genome. As a result, there are a total of 45 KIFs. The nomenclature of all KIFs is presented. To understand the function of KIFs in intracellular transport in a single tissue, we focused on the brain. The expression of 38 KIFs was detected in brain tissue by Northern blotting or PCR using cDNA. The brain, mainly composed of highly differentiated and polarized cells such as neurons and glia, requires a highly complex intracellular transport system as indicated by the increased number of KIFs for their sophisticated functions. It is becoming increasingly clear that the cell uses a number of KIFs and tightly controls the direction, destination, and velocity of transportation of various important functional molecules, including mRNA. This report will set the foundation of KIF and intracellular transport research.

書籍

  • Encyclopedia of Biophysics, Editor Gordon C. Roberts
    Harukata Miki, Nobutaka Hirokawa (担当:分担執筆範囲:Kinesin Superfamily Classification)
    Springer 2013年

MISC



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