Updated on 2024/03/29

写真a

 
FUKUDA Nanaho
 
Organization
Brain Research Institute Center for Bioresources Associate Professor
Title
Associate Professor
External link

Degree

  • 博士(生命科学) ( 2005.3   東京大学 )

Research Interests

  • Molecular biology

  • Neuron

  • Spermatogenesis

  • Gene knockout mice

  • mRNA localization

Research Areas

  • Life Science / Molecular biology

Research History (researchmap)

  • 新潟大学脳研究所   動物資源開発研究分野   准教授

    2022.6

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    Country:Japan

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  • Niigata University   Brain Research Institute Center for Bioresources Bioresource Science Branch Department of Comparative and Experimental Medicine   Lecturer

    2019.4 - 2022.5

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  • Niigata University   Brain Research Institute   Specially Appointed Lecturer

    2018.10 - 2019.3

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  • Niigata University   Brain Research Institute   Assistant Professor

    2018.1 - 2018.10

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  • Nara Institute of Science and Technology   Graduate School of Biological Sciences   Assistant Professor

    2015.9 - 2017.12

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  • Nara Institute of Science and Technology   Graduate School of Biological Sciences

    2014.4 - 2015.9

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  • Nara Institute of Science and Technology   Graduate School of Biological Sciences

    2013.10 - 2014.3

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  • Karolinska Institutet   Researcher

    2011.7 - 2013.9

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  • Karolinska Institutet

    2008.4 - 2011.6

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  • RIKEN   Researcher

    2005.4 - 2008.3

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Research History

  • Niigata University   Brain Research Institute Center for Bioresources   Associate Professor

    2022.6

  • Niigata University   Brain Research Institute Center for Bioresources   Lecturer

    2019.4 - 2022.5

  • Niigata University   Brain Research Institute Center for Bioresources   Specially Appointed Lecturer

    2018.10 - 2019.3

  • Niigata University   Brain Research Institute Center for Bioresources   Assistant Professor

    2018.1 - 2018.10

 

Papers

  • Axonal mRNA binding of hnRNP A/B is crucial for axon targeting and maturation of olfactory sensory neurons Reviewed

    Nanaho Fukuda, Tomoyuki Fukuda, Piergiorgio Percipalle, Kanako Oda, Nobuyuki Takei, Kevin Czaplinski, Kazushige Touhara, Yoshihiro Yoshihara, Toshikuni Sasaoka

    Cell Reports   42 ( 5 )   112398 - 112398   2023.5

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    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.celrep.2023.112398

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  • Temperature imaging using a cationic linear fluorescent polymeric thermometer and fluorescence lifetime imaging microscopy. Reviewed

    Inada N, Fukuda N, Hayashi T, Uchiyama S

    Nature protocols   14 ( 4 )   1293 - 1321   2019.4

  • CTCF contributes in a critical way to spermatogenesis and male fertility Reviewed

    Abrahan Hernandez-Hernandez, Ingrid Lilienthal, Nanaho Fukuda, Niels Galjart, Christer Hoog

    SCIENTIFIC REPORTS   6   28355   2016.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    The CCCTC-binding factor (CTCF) is an architectural protein that governs chromatin organization and gene expression in somatic cells. Here, we show that CTCF regulates chromatin compaction necessary for packaging of the paternal genome into mature sperm. Inactivation of Ctcf in male germ cells in mice (Ctcf-cKO mice) resulted in impaired spermiogenesis and infertility. Residual spermatozoa in Ctcf-cKO mice displayed abnormal head morphology, aberrant chromatin compaction, impaired protamine 1 incorporation into chromatin and accelerated histone depletion. Thus, CTCF regulates chromatin organization during spermiogenesis, contributing to the functional organization of mature sperm.

    DOI: 10.1038/srep28355

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  • A Cell-Permeable Fluorescent Polymeric Thermometer for Intracellular Temperature Mapping in Mammalian Cell Lines Reviewed

    Teruyuki Hayashi, Nanaho Fukuda, Seiichi Uchiyama, Noriko Inada

    PLOS ONE   10 ( 2 )   e0117677   2015.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:PUBLIC LIBRARY SCIENCE  

    Changes in intracellular temperatures reflect the activity of the cell. Thus, the tool to measure intracellular temperatures could provide valuable information about cellular status. We previously reported a method to analyze the intracellular temperature distribution using a fluorescent polymeric thermometer (FPT) in combination with fluorescence lifetime imaging microscopy (FLIM). Intracellular delivery of the FPT used in the previous study required microinjection. We now report a novel FPT that is cell permeable and highly photostable, and we describe the application of this FPT to the imaging of intracellular temperature distributions in various types of mammalian cell lines. This cell-permeable FPT displayed a temperature resolution of 0.05 degrees C to 0.54 degrees C within the range from 28 degrees C to 38 degrees C in HeLa cell extracts. Using our optimized protocol, this cell-permeable FPT spontaneously diffused into HeLa cells within 10 min of incubation and exhibited minimal toxicity over several hours of observation. FLIM analysis confirmed a temperature difference between the nucleus and the cytoplasm and heat production near the mitochondria, which were also detected previously using the microinjected FPT. We also showed that this cell-permeable FPT protocol can be applied to other mammalian cell lines, COS7 and NIH/3T3 cells. Thus, this cell-permeable FPT represents a promising tool to study cellular states and functions with respect to temperature.

    DOI: 10.1371/journal.pone.0117677

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  • STAG3-mediated stabilization of REC8 cohesin complexes promotes chromosome synapsis during meiosis Reviewed

    Tomoyuki Fukuda, Nanaho Fukuda, Ana Agostinho, Abrahan Hernandez-Hernandez, Anna Kouznetsova, Christer Hoog

    EMBO JOURNAL   33 ( 11 )   1243 - 1255   2014.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL  

    Cohesion between sister chromatids in mitotic and meiotic cells is promoted by a ring-shaped protein structure, the cohesin complex. The cohesin core complex is composed of four subunits, including two structural maintenance of chromosome (SMC) proteins, one alpha-kleisin protein, and one SA protein. Meiotic cells express both mitotic and meiosis-specific cohesin core subunits, generating cohesin complexes with different subunit composition and possibly separate meiotic functions. Here, we have analyzed the in vivo function of STAG3, a vertebrate meiosis-specific SA protein. Mice with a hypomorphic allele of Stag3, which display a severely reduced level of STAG3, are viable but infertile. We show that meiocytes in homozygous mutant Stag3 mice display chromosome axis compaction, aberrant synapsis, impaired recombination and developmental arrest. We find that the three different alpha- kleisins present in meiotic cells show different dosage-dependent requirements for STAG3 and that STAG3-REC8 cohesin complexes have a critical role in supporting meiotic chromosome structure and functions.

    DOI: 10.1002/embj.201387329

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  • 細胞の温度を測る Reviewed

    稲田のりこ, 林晃之, 福田七穂, 内山聖一

    バイオイメージング   23   18 - 22   2014

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  • The Transacting Factor CBF-A/Hnrnpab Binds to the A2RE/RTS Element of Protamine 2 mRNA and Contributes to Its Translational Regulation during Mouse Spermatogenesis Reviewed

    Nanaho Fukuda, Tomoyuki Fukuda, John Sinnamon, Abrahan Hernandez-Hernandez, Manizheh Izadi, Chandrasekhar S. Raju, Kevin Czaplinski, Piergiorgio Percipalle

    PLOS GENETICS   9 ( 10 )   2013.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:PUBLIC LIBRARY SCIENCE  

    During spermatogenesis, mRNA localization and translation are believed to be regulated in a stage-specific manner. We report here that the Protamine2 (Prm2) mRNA transits through chromatoid bodies of round spermatids and localizes to cytosol of elongating spermatids for translation. The transacting factor CBF-A, also termed Hnrnpab, contributes to temporal regulation of Prm2 translation. We found that CBF-A co-localizes with the Prm2 mRNA during spermatogenesis, directly binding to the A2RE/RTS element in the 3' UTR. Although both p37 and p42 CBF-A isoforms interacted with RTS, they associated with translationally repressed and de-repressed Prm2 mRNA, respectively. Only p42 was found to interact with the 5' cap complex, and to co-sediment with the Prm2 mRNA in polysomes. In CBF-A knockout mice, expression of protamine 2 (PRM2) was reduced and the Prm2 mRNA was prematurely translated in a subset of elongating spermatids. Moreover, a high percentage of sperm from the CBF-A knockout mouse showed abnormal DNA morphology. We suggest that CBF-A plays an important role in spermatogenesis by regulating stage-specific translation of testicular mRNAs.

    DOI: 10.1371/journal.pgen.1003858

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  • In neurons, activity-dependent association of dendritically transported mRNA transcripts with the transacting factor CBF-A is mediated by A2RE/RTS elements Reviewed

    Chandrasekhar S. Raju, Nanaho Fukuda, Carmen Lopez-Iglesias, Christian Goritz, Neus Visa, Piergiorgio Percipalle

    MOLECULAR BIOLOGY OF THE CELL   22 ( 11 )   1864 - 1877   2011.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER SOC CELL BIOLOGY  

    In neurons certain mRNA transcripts are transported to synapses through mechanisms that are not fully understood. Here we report that the heterogeneous nuclear ribonucleoprotein CBF-A (CArG Box binding Factor A) facilitates dendritic transport and localization of activity-regulated cytoskeleton-associated protein (Arc), brain-derived neurotrophic factor (BDNF), and calmodulin-dependent protein kinase II (CaMKII alpha) mRNAs. We discovered that, in the adult mouse brain, CBF-A has a broad distribution. In the nucleus, CBF-A was found at active transcription sites and interchromosomal spaces and close to nuclear pores. In the cytoplasm, CBF-A localized to dendrites as well as pre- and postsynaptic sites. CBF-A was found in synaptosomal fractions, associated with Arc, BDNF, and CaMKII alpha mRNAs. Electrophoretic mobility shift assays demonstrated a direct interaction mediated via their hnRNP A2 response element (A2RE)/RNA trafficking sequence (RTS) elements located in the 3' untranslated regions. In situ hybridization and microscopy on live hippocampal neurons showed that CBF-A is in dynamic granules containing Arc, BDNF, and CaMKII alpha mRNAs. N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) postsynaptic receptor stimulation led to CBF-A accumulation in dendrites; increased Arc, BDNF, and CaMKII alpha mRNA levels; and increased amounts of transcripts coprecipitating with CBF-A. Finally, CBF-A gene knockdown led to decreased mRNA levels. We propose that CBF-A cotranscriptionally binds RTSs in Arc, BDNF, and CaMKII alpha mRNAs and follows the transcripts from genes to dendrites, promoting activity-dependent nuclear sorting of transport-competent mRNAs.

    DOI: 10.1091/mbc.E10-11-0904

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  • Actin-associated hnRNP proteins as transacting factors in the control of mRNA transport and localization Reviewed

    Piergiorgio Percipalle, Chandrasekhar S. Raju, Nanaho Fukuda

    RNA BIOLOGY   6 ( 2 )   171 - 174   2009.4

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    Language:English   Publisher:LANDES BIOSCIENCE  

    Upon nuclear export, RNP particles are either localized to polysomes or further assembled into larger RNA granules which are transported to the cellular periphery for localized translation. These mechanisms are important for asymmetric mRNA and protein distribution and have profound impact on cellular physiology. mRNA transport and localization requires cis-acting elements and cellular transacting factors. hnRNP A2 functions as transacting factor for MBP mRNA transport in myelin-producing oligodendrocytes processes through a mechanism of direct RTS recognition. Here we examine the molecular mechanisms which regulate MBP mRNA transport in mouse oligodendrocytes in view of the recent discovery of CBF-A as novel transacting factor. CBF-A is highly conserved and in humans it is referred to as hnRNP A/B. Since actin has a key role in mRNA biogenesis and it is associated with both CBF-A and hnRNP A2 in pre-mRNP/mRNP complexes, we discuss integrative models underscoring the importance of actin-associated hnRNPs in mRNA biogenesis control at the post-transcriptional level.

    DOI: 10.4161/rna.6.2.8195

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  • Decreased olfactory mucus secretion and nasal abnormality in mice lacking type 2 and type 3 IP3 receptors Reviewed

    Nanaho Fukuda, Mika Shirasu, Koji Sato, Etsuko Ebisui, Kazushige Touhara, Katsuhiko Mikoshiba

    EUROPEAN JOURNAL OF NEUROSCIENCE   27 ( 10 )   2665 - 2675   2008.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL  

    Although nasal mucus is thought to play important roles in the mammalian olfactory system, the mechanisms of secretion of it and its physiological roles are poorly understood. Here we show that type 2 and type 3 IP3 receptors (IP3R2 and IP3R3) play critical roles in olfactory mucus secretion. Histological studies showed that IP3R2 and IP3R3 are predominantly expressed in two types of nasal glands, the anterior glands of the nasal septum and the lateral nasal glands (LNG), which contain mucosal proteins secreted to the main olfactory epithelium. We therefore examined LNG acinar cells, and found that acetylcholine-mediated calcium responses and fluid- and protein- secretion in the acinar cells were markedly decreased in IP3R2-R3 double-knockout (KO) mice. We also found nasal inflammation and a decrease in olfactory capacity in IP3R2-R3 KO mice. Despite intact signal transduction in the olfactory epithelium, IP3R2-R3 KO mice exhibited elevated threshold sensitivity to odorants on in vivo imaging of olfactory glomerular responses and behavioral tests. Our findings suggest that IP3R2 and IP3R3 mediate nasal mucus secretion, which is important for the maintenance of nasal tissue as well as the perception of odors.

    DOI: 10.1111/j.1460-9568.2008.06240.x

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  • Developmental expression patterns of testicular olfactory receptor genes during mouse spermatogenesis Reviewed

    N Fukuda, K Touhara

    GENES TO CELLS   11 ( 1 )   71 - 81   2006.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BLACKWELL PUBLISHING  

    A subset of olfactory receptors (ORs) is expressed in mammalian male germ cells. Recent studies on human and mouse sperm have suggested that calcium signaling via a testicular OR regulates sperm flagellar motility. However, it remains to be determined at what stages testicular ORs are expressed during spermatogenesis and whether each germ cell expresses one or multiple ORs. Here we examined the developmental expression profiles of several mouse testicular OR genes using an in situ hybridization technique at the cellular level. We found that OR transcripts in the spermatogenic cells are expressed in three developmental stages: late pachyten spermatocytes, early round spermatids, or late round spermatids. The OR mRNAs were condensed in a single dot-like structure within the nuclei of a subpopulation of spermatogenic cells. Double-fluorescent in situ hybridization revealed that some cells contained two dot-like signals derived from transcripts of two different ORs, suggesting that single spermatogenic cells could express more than one OR. One cell-multiple OR gene expression combined with variability in expression appears to result in heterogeneity in the repertoire of ORs expressed by individual spermatogenic cells. Although the functional consequence of heterogeneous OR expression awaits development of a methodology for characterizing OR proteins, our observations give insights into OR gene expression as well as OR function(s) in spermatogenic cells.

    DOI: 10.1111/j.1365-2443.2005.00915.x

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  • Functional characterization of a mouse testicular olfactory receptor and its role in chemosensing and in regulation of sperm motility Reviewed

    N Fukuda, K Yomogida, M Okabe, K Touhara

    JOURNAL OF CELL SCIENCE   117 ( 24 )   5835 - 5845   2004.11

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:COMPANY OF BIOLOGISTS LTD  

    Although a subset of the olfactory receptor (OR) gene family is expressed in testis, neither their developmental profile nor their physiological functions have been fully characterized. Here, we show that MOR23 (a mouse OR expressed in the olfactory epithelium and testis) functions as a chemosensing receptor in mouse germ cells. In situ hybridization showed that MOR23 was expressed in round spermatids during stages VI-BIII of spermatogenesis. Lyral, a cognate ligand of MOR23, caused an increase in intracellular Ca2+ in a fraction of spermatogenic cells and spermatozoa. We also generated transgenic mice that express high levels of MOR23 in the testis and examined the response of their germ cells to lyral. The results provided evidence that lyral-induced Ca2+ increases were indeed mediated by MOR23. In a sperm accumulation assay, spermatozoa migrated towards an increasing gradient of lyral. Tracking and sperm flagellar analyses suggest that Ca2+ increases caused by MOR23 activation lead to modulation of flagellar configuration, resulting in chemotaxis. By contrast, a gradient of a cAMP analog or K8.6 solution, which elicit Ca2+ influx in spermatozoa, did not cause sperm accumulation, indicating that chemosensing and regulation of sperm motility was due to an OR-mediated local Ca2+ increase. The present studies indicate that mouse testicular ORs might play a role in chemoreception during sperm-egg communication and thereby regulate fertilization.

    DOI: 10.1242/jcs.01507

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  • Function of olfactory receptors in non-olfactory tissues Reviewed

    N Fukuda, K Touhara

    SEIKAGAKU   76 ( 11 )   1462 - 1466   2004.11

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    Language:Japanese   Publisher:JAPANESE BIOCHEMICAL SOC  

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MISC

  • Regulation of sperm motility via a testicular olfactory receptor in mice

    Nanaho Fukuda, Kazushige Touhara

    ZOOLOGICAL SCIENCE   21 ( 12 )   1219 - 1219   2004.12

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    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:ZOOLOGICAL SOC JAPAN  

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  • Functional characterization of a mouse testicular olfactory receptor and its role in cheimosenseng and regulation of sperm motility

    Nanaho Fukuda, Kentaro Yomogida, Masaru Okabe, Kazushige Touhara

    ZOOLOGICAL SCIENCE   21 ( 12 )   1285 - 1285   2004.12

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  • 嗅覚受容体は鼻以外で機能しているか?

    福田七穂

    生化学   2004