論文 - 木村　俊介

Diversity of the intestinal microbiota differently affects non-neuronal and atropine-sensitive ileal contractile responses to short-chain fatty acids in mice.

Yajima M, Karaki SI, Tsuruta T, Kimura S, Nio-Kobayashi J, Kuwahara A, Yajima T

Biomedical research (Tokyo, Japan) （BIOMEDICAL RESEARCH PRESS LTD）  37 （ 5 ） 319 - 328 2016年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0388-6107

　概要を見る

Non-neuronal and atropine-sensitive ileal contractile responses to short chain fatty acids (SCFAs) are detected in the neonatal stage, and change with age or inflammatory conditions. However, the roles of luminal SCFAs in developmental changes have not yet been elucidated. We examined ileal contractile responses to SCFAs in mice colonized with different SCFA-producing intestinal microbiota under normal and inflammatory conditions. Using conventional (Conv), germ-free (GF), and gnotobiotic mice infected with Bifidobacterium (GB-bif), Propionibacterium (GB-prop), or Lactobacillus (GB-lact), ileal contractions were measured in 1-day-old neonates and 7-week-old mice using an isotonic transducer. Contractions occurred in all 1-day-old neonates, and were significantly desensitized in the adult stage in the Conv, GB-bif, and GB-prop groups, but not in the GF and GB-lact groups. An injection of lipopolysaccharide frequently restored desensitized contractions; however, the contraction rate did not change in the GF and GB-lact groups. The relative mRNA expression of a SCFA receptor (GPR43) or nicotinic acetylcholine receptor alpha 7 was weaker in the GF group (0.3-fold or 0.4-fold expression level, respectively) than in the Conv group. In conclusion, the luminal inhabitation of SCFA-producing bacteria may potentiate the regulation of non-neuronal and atropine-sensitive ileal contractile responses to SCFAs under healthy and inflammatory conditions.

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The selective distribution of LYVE-1-expressing endothelial cells and reticular cells in the reticulo-endothelial system (RES).

Zheng M, Kimura S, Nio-Kobayashi J, Iwanaga T

Biomedical research (Tokyo, Japan) （BIOMEDICAL RESEARCH PRESS LTD）  37 （ 3 ） 187 - 198 2016年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0388-6107

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LYVE-1, a receptor molecule for hyaluronan, is expressed in the lymphatic endothelium, blood sinus endothelium, and certain macrophage lineages. The present immunohistochemical study revealed a broader distribution of LYVE-1 in vascular endothelial cells of the murine lung, adrenal gland, and heart as well as the liver and spleen. In addition, sinus reticular cells-including sinuslining cells-in the medulla of the lymph node also intensely expressed LYVE-1. Ultrastructurally, immuno-gold particles for LYVE-1 were localized on the entire length of plasma membrane in all cell types. Most of these LYVE-1-expressing cells had previously been classified as the reticuloendothelial system (RES) specialized for eliminating foreign particles. An LPS stimulation decreased the LYVE-1 expression in macrophages but elevated the expression at mRNA and protein levels in the liver and lung, major organs for the elimination of blood-born waste substances. LYVE-1-expressing endothelial cells in these organs participated in the endocytosis of exogenous particles, and the uptake ability was conspicuously enhanced by the LPS challenge. Although the expression of the degrading enzyme, hyaluronidase, was generally low in the LYVE-1-expressing cells, they were topographically associated with a dense distribution of macrophages possessing hyaluronidase activities in each tissue. These findings suggest that the LYVE-1-expressing cells might be involved in the uptake of hyaluronan and other waste products as well as foreign particles circulating in the blood and lymph while participating in the subsequent degradation in relay with adjacent macrophage populations.

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The broad distribution of GP2 in mucous glands and secretory products.

Kimura S, Nio-Kobayashi J, Kishimoto A, Iwanaga T

Biomedical research (Tokyo, Japan) （BIOMEDICAL RESEARCH PRESS LTD）  37 （ 6 ） 351 - 358 2016年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0388-6107

　概要を見る

GP2, a GPI-anchored glycoprotein that is a useful marker for M cells of Peyer's patches, is functionally related to the uptake of pathogenic bacteria in the gut lumen. Our immunostaining throughout the whole body of mice detected a broader localization than previously found of GP2 in various mucous glands and secretory cells. In the oral cavity, the palatine gland and lingual gland intensely expressed GP2 with immunolabeling along the basolateral membrane of acini and in luminal secretions of ducts. Secretory portions of the duodenal gland as well as the pancreas were immunoreactive for GP2 in the digestive tract. Luminal contents in the small intestine contained aggregations of GP2-immunoreactive substances which mixed with bacteria. The bulbourethral gland of Cowper displayed the GP2 immunoreactivity among the male reproductive organs. The vaginal epithelium contained many GP2-immunoreactive goblet-like cells, the occurrence of which dramatically changed according to the estrous cycle. These findings show that GP2 is a popular secretory product released from mucous glands and secretory cells and may support defense mechanisms against pathogenic bacteria in the tubular organs open to the external milieu.

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Epithelium-Intrinsic MicroRNAs Contribute to Mucosal Immune Homeostasis by Promoting M-Cell Maturation.

Nakato G, Hase K, Sato T, Kimura S, Sakakibara S, Sugiyama M, Obata Y, Hanazato M, Iwanaga T, Ohno H

PloS one （PUBLIC LIBRARY SCIENCE）  11 （ 3 ） e0150379 2016年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1932-6203

　概要を見る

cells in the follicle-associated epithelium (FAE) of Peyer's patches (PPs) serve as a main portal for external antigens and function as a sentinel in mucosal immune responses. The scarcity of these cells has hampered identification of M cell-specific molecules. Recent efforts have begun to provide insight into antigen transcytosis and differentiation of M cells; however, the molecular mechanisms underlying these processes are not fully elucidated. Small non-coding RNAs including microRNA (miRNA) have been reported to regulate gene expression and control various biological processes such as cellular differentiation and function. To evaluate the expression of miRNAs in FAE, including M cells, we previously performed microarray analysis comparing intestinal villous epithelium (VE) and PP FAE. Here we confirmed FAE specific miRNA expression levels by quantitative PCR. To gain insight into miRNA function, we generated mice with intestinal epithelial cell-specific deletion of Dicer1 (Dicer(Delta IEC)) and analyzed intestinal phenotypes, including M-cell differentiation, morphology and function. Dicer(Delta IEC) mice had a marked decrease in M cells compared to control floxed Dicer mice, suggesting an essential role of miRNAs in maturation of these cells. Furthermore, transmission electron microscopic analysis revealed that depletion of miRNA caused the loss of endosomal structures in M cells. In addition, antigen uptake by M cells was impaired in Dicer(Delta IEC) mice. These results suggest that miRNAs play a significant role in M cell differentiation and help secure mucosal immune homeostasis.

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Non‐neuronal, but atropine‐sensitive ileal contractile responses to short‐chain fatty acids: age‐dependent desensitization and restoration under inflammatory conditions in mice

M Yajima, S Kimura, S Karaki, J Nio‐Kobayashi, T Tsuruta, A Kuwahara, ...

Physiological reports 4 (7), e12759 2016年

RANKL regulates differentiation of microfold cells in mouse nasopharynx-associated lymphoid tissue (NALT).

Mutoh M, Kimura S, Takahashi-Iwanaga H, Hisamoto M, Iwanaga T, Iida J

Cell and tissue research （SPRINGER）  364 （ 1 ） 175 - 84 2015年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0302-766X

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Murine nasopharynx-associated lymphoid tissue (NALT), located at the base of the nasal cavity, serves as a major site for the induction of mucosal immune responses against airway antigens. The follicle-associated epithelium (FAE) covering the luminal surface of NALT is characterized by the presence of microfold cells (M cells), which take up and transport luminal antigens to lymphocytes. Glycoprotein 2 (GP2) has recently been identified as a reliable marker for M cells in Peyer's patches of the intestine. However, the expression of GP2 and other functional molecules in the M cells of NALT has not yet been examined. We have immunohistochemically detected GP2-expressing cells in the FAE of NALT and the simultaneous expression of other intestinal M-cell markers, namely Tnfaip2, CCL9, and Spi-B. These cells have been further identified as M cells because of their higher uptake capacity of luminal microbeads. Electron microscopic observations have shown that GP2-expressing cells on the FAE display morphological features typical of M cells: they possess short microvilli and microfolds on the luminal surface and are closely associated with intraepithelial lymphocytes. We have also found that the receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed by stromal cells underneath the FAE, which provides its receptor RANK. The administration of RANKL markedly increases the number of GP2(+)Tnfaip2(+) cells on the NALT FAE and that of intestinal M cells. These results suggest that GP2(+)Tnfaip2(+) cells in NALT are equivalent to intestinal M cells, and that RANKL-RANK signaling induces their differentiation.

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鼻咽頭粘膜組織における抗原取り込み細胞であるM細胞分化機構の解析

武藤 麻未, 木村 俊介, 吉沢 早織, 岩永 敏彦, 飯田 順一郎

日本矯正歯科学会大会プログラム・抄録集 （(公社)日本矯正歯科学会）  74回   191 - 191 2015年11月

共著

Regulated C-C motif ligand 2 (CCL2) in luteal cells contributes to macrophage infiltration into the human corpus luteum during luteolysis.

Nio-Kobayashi J, Kudo M, Sakuragi N, Kimura S, Iwanaga T, Duncan WC

Molecular human reproduction （OXFORD UNIV PRESS）  21 （ 8 ） 645 - 654 2015年05月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1360-9947

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Intense macrophage infiltration is observed during luteolysis in various animals including women; however, we still do not know how macrophage infiltration into the human corpus luteum (CL) during luteolysis is regulated. In this study, we examined the expression, localization and regulation of an important chemokine for the recruitment of monocyte/macrophage lineages, C-C motif ligand 2 (CCL2), in the human CL across the luteal phase and in cultured human luteinized granulosa cells (LGCs), with special reference to the number of infiltrating macrophages and luteal cell function. CCL2 mRNA increased in the non-functional regressing CL during menstruation (P < 0.01), corresponding to an elevated mRNA expression of a macrophage-derived cytokine, tumor necrosis factor (TNF), and an increased number of infiltrating macrophages positively stained with a macrophage marker, CD68. CCL2 protein was immunohistochemically localized to the cytoplasm of granulosa-lutein and theca-lutein cells, and CCL2 mRNA was significantly reduced by hCG both in vivo (P < 0.05) and in vitro (P < 0.01). CCL2 was also down-regulated by luteotrophic prostaglandin (PG) E (P < 0.0001), but up-regulated by luteolytic PGF (P < 0.05) in vitro. Administration of TNF significantly enhanced the CCL2 mRNA expression in cultured LGCs (P < 0.01). A greater abundance of infiltrating macrophages were found around granulosa-lutein cells lacking 3 beta-HSD or PGE synthase (PGES) immunostaining. CCL2 mRNA expression was negatively correlated with both HSD3B1 and PGES, suggesting that locally produced progesterone and PGE suppress macrophage infiltration into the CL. Taken together, the infiltration of macrophages in the human CL is regulated by endocrine and paracrine molecules via regulation of the CCL2 expression in luteal cells.

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Visualization of the entire differentiation process of murine M cells: suppression of their maturation in cecal patches.

Kimura S, Yamakami-Kimura M, Obata Y, Hase K, Kitamura H, Ohno H, Iwanaga T

Mucosal immunology （NATURE PUBLISHING GROUP）  8 （ 3 ） 650 - 660 2015年05月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1933-0219

　概要を見る

粘膜組織の各部位に存在するリンパ濾胞は管腔内の抗原に対するIgA抗体を産生し、粘膜免疫応答の主役となるリンパ性器官である。リンパ濾胞上皮に存在するM細胞は異物を取込むことで、粘膜免疫応答の開始に働く特殊な上皮細胞である。
我々は濾胞上皮のホールマウント染色法を開発し、成熟M細胞と未成熟M細胞の可視化に成功した。そして、転写因子RelBの活性がM細胞の分化に必須であったことから、RelB活性の制御がM細胞成熟に重要であることを見出した。

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GP2-expressing cells in the conjunctiva and tear ducts of mice: identification of a novel type of cells in the squamous stratified epithelium.

Kimura S, Kishimoto A, Mutoh M, Takahashi-Iwanaga H, Iwanaga T

Biomedical research (Tokyo, Japan) （BIOMEDICAL RESEARCH PRESS LTD）  36 （ 4 ） 263 - 272 2015年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0388-6107

　概要を見る

GP2 is a membrane-associated secretory protein originally identified in zymogen granules of pancreatic acinar cells. Recently, this glycoprotein has attracted attention as a marker substance of M cells of Peyer's patches and for its involvement in the selective uptake of pathological bacteria via M cells. When we stained the conjunctiva and tear ducts of mice using a GP2 antibody, all goblet cells in the squamous stratified epithelium of the conjunctiva were intensely immunolabeled, while goblet cells in the intestine and airway were devoid of the immunoreactivity, indicating that the conjunctiva contains a special type of goblet cell. Further immunostaining for GP-2 labeled dispersed cells of peculiar shapes within the stratified squamous epithelium in the lacrimal canaliculi, lacrimal sac, and nasolacrimal duct. The GP2-immunoreactive cells in the tear duct projected arched or branched processes toward the basement membrane. Electron-microscopically, immunogold particles for GP2 outlined the basolateral plasma membrane of both the conjuntival goblet cells and the peculiarly shaped cells in the tear duct. Intracellularly, GP2 products of the goblet cells were localized around secretory granules in the apical cytoplasm and those of the tear duct cells inside the vesicles. The luminal contents close to apical plasma membrane were heavily labeled with immunogold particles, suggesting an exocytosis-based targeting of GP2 to the plasma membrane and its release into the lumen. The possible function of GP2 in tear ducts is discussed in relation to a defense system against invasive microoranisms and antigens.

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Epithelial-stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues.

Obata Y, Kimura S, Nakato G, Iizuka K, Miyagawa Y, Nakamura Y, Furusawa Y, Sugiyama M, Suzuki K, Ebisawa M, Fujimura Y, Yoshida H, Iwanaga T, Hase K, Ohno H

EMBO reports （WILEY-BLACKWELL）  15 （ 12 ） 1297 - 1304 2014年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1469-221X

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Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpja gene encoding a transcription factor implicated in Notch signalingin intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE.

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A novel type of cells expressing GP2 in the respiratory epithelium of the paranasal sinuses in mice.

Kimura S, Muto M, Hisamoto M, Zheng M, Iwanaga T

Biomedical research (Tokyo, Japan) （BIOMEDICAL RESEARCH PRESS LTD）  35 （ 5 ） 329 - 337 2014年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0388-6107

　概要を見る

GP2, a GPI-anchored glycoprotein, is a useful marker of M cells in Peyer's patches. Our immunostaining of the paranasal sinuses in mice detected a condensed distribution of GP2-immunoreactive cells within the epithelium, apart from lymphoid tissues. In the paranasal sinuses, the cells exhibited a unique morphology characterized by a slender neck portion and huge terminal bulb, quite different from M cells. Electron microscopically, the GP2 immunoreactivity centered on the luminal plasma membrane of the terminal bulb, being less intense in the baso-lateral plasma membrane and not visible at all in the cytoplasm. The cells frequently came in contact with nerve fibers containing small synaptic vesicles. These nerve fibers contained neither CGRP nor substance P indicators of sensory neurons; moreover, no signal molecules used for a sensory function were expressed in the GP2-immunoreactive cells, implying that these nerves are efferent in nature. A weak but significant stainability in PAS reaction and an intense GP2 immunoreactivity for typical goblet cells in the tunica conjunctiva suggest that the GP2-expressing cells in paranasal sinuses are in the lineage of goblet cells.

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Three types of macrophagic cells in the mesentery of mice with special reference to LYVE-1-immunoreactive cells.

Zheng M, Kimura S, Nio-Kobayashi J, Takahashi-Iwanaga H, Iwanaga T

Biomedical research (Tokyo, Japan) （BIOMEDICAL RESEARCH PRESS LTD）  35 （ 1 ） 37 - 45 2014年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0388-6107

　概要を見る

Immunohistochemistry using whole mount preparations of the murine mesentery revealed two types of LYVE-1-immunoreactive cells with dendritic morphology other than F4/80(+) typical macrophages. The two types of LYVE-1(+) cells were regularly distributed with constant intervals throughout the mesentery and appeared to possess their own territory. Both types of LYVE-1(+) cells were weakly or moderately immunopositive for F4/80 antibody, a marker of macrophages, while F4/80(+) round macrophages were absolutely free from the LYVE-1 immunoreactivity. Only macrophages could ingest latex particles of 20 nm in diameter 3 h after a peritoneal injection. Peritoneal administration of lipopolysaccharide (LPS) induced a rapid reduction of LYVE-1 immunoreactivity in the cells with dendritic morphology followed by an increased immunoreactivity to F4/80 antibody, and simultaneously by dynamic changes in their shape. Under nonnal conditions, F4/80(+) macrophages in various connective tissues expressed LYVE-1, in contrast to lack of LYVE-1 in F4/80(+) macrophages within the parenchyma of visceral organs and macrophages residing in hepatic sinusoids and pulmonary alveoli. LYVE-1 may play a role in cell adhesion and migration of macrophagic cells within connective tissues rich in hyaluronan, and loss of LYVE-1 becomes a reliable sign of activated conditions in inflammation.

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Epithelial–stromal interaction via N otch signaling is essential for the full maturation of gut‐associated lymphoid tissues

Y Obata, S Kimura, G Nakato, K Iizuka, Y Miyagawa, Y Nakamura, ...

EMBO reports 15 (12), 1297-1304 2014年

Ubiquitin-specific protease 2-69 in macrophages potentially modulates metainflammation.

Kitamura H, Kimura S, Shimamoto Y, Okabe J, Ito M, Miyamoto T, Naoe Y, Kikuguchi C, Meek B, Toda C, Okamoto S, Kanehira K, Hase K, Watarai H, Ishizuka M, El-Osta A, Ohara O, Miyoshi I

FASEB journal : official publication of the Federation of American Societies for Experimental Biology （FEDERATION AMER SOC EXP BIOL）  27 （ 12 ） 4940 - 4953 2013年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0892-6638

　概要を見る

Macrophages play a critical role in chronic inflammation and metabolic diseases. We identified a longer splice variant of ubiquitin specific protease (USP) 2-69 as a novel molecule that modulates pathways implicated in metabolic disorders. Expression levels of aP2/ FABP4 and PAI-1/SERPINE1 genes were increased by 4- and 1.8-fold, respectively, after short hairpin RNA-mediated knockdown (KD) of the USP2 gene, and such expression was alleviated by overexpression of USP2-69 in human myeloid cell lines. Supernatants derived from USP2-KD cells induced IL6 (6-fold) and SAA3 (15-fold) in 3T3-L1 adipocytes to suggest the anti-inflammatory properties of USP2. In addition, we observed a 30% decrease in the number of macrophages in mesenteric adipose tissue derived from USP2-69 transgenic mice fed a high-fat diet for 14 wk compared with that in their C57BL/6 littermates (P&lt
0.01), which was consistent with a 40% decrease in transcription of aP2 and PAI-1. The aP2 locus exhibited elevated chromatin accessibility (&gt
2.1-fold), methylation of histone H3 lysine 4 (&gt
4.5- fold), and acetylation of histone H4 (&gt
2.5-fold) in USP2-KD cells. Transfection of isopeptidase-mutated USP2-69 did not alter chromatin conformation on the aP2 locus in USP2-KD cells. Our results suggest that USP2-69 suppresses meta-inflammatory molecules involved in the development of type-2 diabetes.-Kitamura, H., Kimura, S., Shimamoto, Y., Okabe, J., Ito, M., Miyamoto, T., Naoe, Y., Kikuguchi, C., Meek, B., Toda, C., Okamoto, S., Kanehira, K., Hase, K., Watarai, H., Ishizuka, M., El-Osta, A., Ohara, O., Miyoshi, I. Ubiquitin-specific protease 2-69 in macrophages potentially modulates metainflammation. © FASEB.

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Beneficial effects of Brazilian propolis on type 2 diabetes in ob/ob mice: Possible involvement of immune cells in mesenteric adipose tissue.

Kitamura H, Naoe Y, Kimura S, Miyamoto T, Okamoto S, Toda C, Shimamoto Y, Iwanaga T, Miyoshi I

Adipocyte 2 （ 4 ） 227 - 236 2013年10月

共著, 査読有り,  ISSN  2162-3945

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Ubiquitin‐specific protease 2‐69 in macrophages potentially modulates metainflammation

H Kitamura, S Kimura, Y Shimamoto, J Okabe, M Ito, T Miyamoto, Y Naoe, ...

The FASEB Journal 27 (12), 4940-4953 2013年

The molecular basis of induction and formation of tunneling nanotubes.

Kimura S, Hase K, Ohno H

Cell and tissue research （SPRINGER）  352 （ 1 ） 67 - 76 2012年11月

共著, 査読有り,  ISSN  0302-766X

　概要を見る

Tunneling nanotubes (TNTs) and associated structures are recently recognized structures for intercellular communication. They are F-actin-containing thin protrusions of the plasma membrane of a cell and allow a direct physical connection to the plasma membranes of remote cells. TNTs and associated structures serve as mediators for intercellular transfer of organelles as well as membrane components and cytoplasmic molecules. Moreover, several pathogens have been shown to exploit these structures to spread among cells. Because of their contribution to normal cellular functions and importance in pathological conditions, studies on TNTs and related structures have accelerated over the past few years. These studies have revealed key molecules for their induction and/or formation; HIV Nef and M-Sec can induce the formation of TNTs in coordination with the remodeling of the actin cytoskeleton and vesicle trafficking.

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Tunneling nanotubes: emerging view of their molecular components and formation mechanisms.

Kimura S, Hase K, Ohno H

Experimental cell research （14）  318 （ 14 ） 1699 - 1706 2012年08月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0014-4827

　概要を見る

Cell-to-cell communication is essential for the development and maintenance of multicellular organisms. The tunneling nanotube (TNT) is a recently recognized distinct type of intercellular communication device. This are thin protrusions of the plasma membrane and allow direct physical connections of the plasma membranes between remote cells. The proposed functions for TNTs include the cell-to-cell transfer of large cellular structures such as membrane vesicles and organelles, as well as signal transduction molecules in a wide variety of cell types. Moreover TNT and TNT-related structures are thought to facilitate the intercellular spreading of virus and/or pathogenic proteins. Despite their contribution to normal cellular functions and importance in pathological conditions, virtually nothing is known about the molecular basis for their formation. We have recently shown that M-Sec (also called TNFaip2) is a key molecule for TNT formation. In cooperation with the RalA small GTPase and the exocyst complex, M-Sec can induce the formation of functional TNTs, indicating that the remodeling of the actin cytoskeleton and vesicle trafficking are involved in M-Sec-mediated TNT formation. Discovery of the role of M-Sec will accelerate our understanding of TNTs, both at the molecular and physiological levels. (C) 2012 Elsevier Inc. All rights reserved.

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Roles of a macrophage molecule M-mod in type 2 diabetes

H Kitamura, M Ito, S Kimura, Y Shimamoto, T Miyamoto, H Watarai, ...

The FASEB Journal 26 (1_supplement), 686.5-686.5 （FEDERATION AMER SOC EXP BIOL）  26 2012年

共著, 査読有り,  ISSN  0892-6638