Lipid bilayers, including those of the plasma membrane and the membrane-enclosed compartments along the secretory and endocytic pathways, exhibit asymmetric lipid distributions. The asymmetric distributions are generated and regulated by flippases (P4-ATPases), floppases (ABC transporters), and scramblases. Spatio-temporal regulation of the lipid asymmetry is critical for many biological processes, such as apoptotic cell death, platelet coagulation, fusion of muscle cells, cytokinesis, cell migration, sperm capacitation and intracellular membrane trafficking. However, the molecular mechanism is largely unknown. We aim to elucidate that how spatio-temporal lipid composition changes are regulated and how such changes regulate cellular function and further homeostasis of organisms.
Research Areas
Life sciences, Cell biology
Papers
The interaction of ATP11C-b with ezrin contributes to its polarized localization
Phospholipid flippase activities and substrate specificities of human type IV P-type ATPases localized to the plasma membrane (vol 289, pg 33543, 2014)
ATP9B, a P4-ATPase (a putative aminophospholipid translocase), localizes to the trans-Golgi network in a CDC50 protein-independent manner (vol 286, pg 38159, 2011)
Redundant roles of BIG2 and BIG1, guanine-nucleotide exchange factors for ADP-ribosylation factors in membrane traffic between the trans-Golgi network and endosomes
Ray Ishizaki; Hye-Won Shin; Hiroko Mitsuhashi; Kazuhisa Nakayama
MOLECULAR BIOLOGY OF THE CELL, Jun. 2008, Peer-reviewed, Lead author
Recruitment of Tom1L1/Srcasm to Endosomes and the Midbody by Tsg101
Proceedings of the National Academy of Sciences of the United States of America, 17 Oct. 2006, Peer-reviewed
AMY-1 (associate of Myc-1) localization to the trans-Golgi network through interacting with BIG2, a guanine-nucleotide exchange factor for ADP-ribosylation factors
Ray Ishizaki; Hye-Won Shin; Sanae M. M. Iguchi-Ariga; Hiroyoshi Ariga; Kazuhisa Nakayama
GENES TO CELLS, Aug. 2006, Peer-reviewed
Erratum: Cellular and subcellular localization of EFA6C, a third member of the EFA6 family, in adult mouse Purkinje cells (Journal of Neurochemistry (2005) 93 (674-85))
Journal of Neurochemistry, Nov. 2005, Peer-reviewed
Roles of ARFRP1 (ADP-ribosylation factor-related protein 1) in post-Golgi membrane trafficking
HW Shin; H Kobayashi; M Kitamura; S Waguri; T Suganuma; Y Uchiyama; K Nakayama
JOURNAL OF CELL SCIENCE, Sep. 2005, Peer-reviewed, Lead author
An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway
HW Shin; M Hayashi; S Christoforidis; S Lacas-Gervais; S Hoepfner; MR Wenk; J Modregger; S Uttenweiler-Joseph; M Wilm; A Nystuen; WN Frankel; M Solimena; P De Camilli; M Zerial
JOURNAL OF CELL BIOLOGY, Aug. 2005, Peer-reviewed, Lead author
Role of ARFRP1 (ADP-ribosylation factor-related protein 1) in post-Golgi membrane traffic
BIG2, a guanine nucleotide exchange factor for ADP-ribosylation factors: Its localization to recycling endosomes and implication in the endosome integrity
HW Shin; N Morinaga; M Noda; K Nakayama
MOLECULAR BIOLOGY OF THE CELL, Dec. 2004, Peer-reviewed, Lead author
Guanine nucleotide-exchange factors for Arf GTPases: Their diverse functions in membrane traffic
HW Shin; K Nakayama
JOURNAL OF BIOCHEMISTRY, Dec. 2004, Peer-reviewed, Invited, Lead author
Dual control of membrane targeting by Ptdlns(4)P and ARF
HW Shin; K Nakayama
TRENDS IN BIOCHEMICAL SCIENCES, Oct. 2004, Peer-reviewed, Invited, Lead author
GAT (GGA and Tom1) domain responsible for ubiquitin binding and ubiquitination
Y Shiba; Y Katoh; T Shiba; K Yoshino; H Takatsu; H Kobayashi; HW Shin; S Wakatsuki; K Nakayama
JOURNAL OF BIOLOGICAL CHEMISTRY, Feb. 2004, Peer-reviewed
GAT (GGA and Tom1) domain responsible for ubiquitin binding and ubiquitination
Y Shiba; Y Katoh; T Shiba; K Yoshino; H Takatsu; H Kobayashi; HW Shin; S Wakatsuki; K Nakayama
JOURNAL OF BIOLOGICAL CHEMISTRY, Feb. 2004, Peer-reviewed
Phosphoinositides regulate membrane-dependent actin assembly by latex bead phagosomes
H Defacque; E Bos; B Garvalov; C Barret; C Roy; P Mangeat; HW Shin; Rybin, V; G Griffiths
MOLECULAR BIOLOGY OF THE CELL, Apr. 2002, Peer-reviewed
gamma-adaptin interacts directly with rabaptin-5 through its ear domain
Y Shiba; H Takatsu; HW Shin; K Nakayama
JOURNAL OF BIOCHEMISTRY, Mar. 2002, Peer-reviewed
Similar subunit interactions contribute to assembly of clathrin adaptor complexes and COPI complex: Analysis using yeast three-hybrid system
H Takatsu; M Futatsumori; K Yoshino; Y Yoshida; HW Shin; K Nakayama
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Jun. 2001, Peer-reviewed
Identification and characterization of novel isoforms of COPI subunits
M Futatsumori; K Kasai; H Takatsu; FW Shin; K Nakayama
JOURNAL OF BIOCHEMISTRY, Nov. 2000, Peer-reviewed
Dynamin II is involved in endocytosis but not in the formation of transport vesicles from the trans-Golgi network
K Kasai; HW Shin; C Shinotsuka; K Murakami; K Nakayama
JOURNAL OF BIOCHEMISTRY, Apr. 1999, Peer-reviewed
Intermolecular and interdomain interactions of a dynamin-related GTP-binding protein, Dnm1p/Vps1p-like protein
HW Shin; H Takatsu; H Mukai; E Munekata; K Murakami; K Nakayama
JOURNAL OF BIOLOGICAL CHEMISTRY, Jan. 1999, Peer-reviewed, Lead author
Identification and characterization of novel clathrin adaptor-related proteins
H Takatsu; M Sakurai; HW Shin; K Murakami; K Nakayama
JOURNAL OF BIOLOGICAL CHEMISTRY, Sep. 1998, Peer-reviewed
Identification and subcellular localization of a novel mammalian dynamin-related protein homologous to yeast Vps1p and Dnm1p
HW Shin; C Shinotsuka; S Torii; K Murakami; K Nakayama
JOURNAL OF BIOCHEMISTRY, Sep. 1997, Peer-reviewed, Lead author
Misc.
Regulation mechanism of phosphatidylserine-flippase at the plasma membrane
Hye-Won Shin; Hiroyuki Takatsu
Seikagaku, 2018, Invited, Lead author, Corresponding author
Membrane curvature generation by transbilayer lipid flip-flop
Hye-Won Shin
実験医学, 2018, Invited
Roles of small GTPases and BAR domain proteins in post-Golgi membrane traffic
Hye-Won Shin; Zhiqiu Man; Kazuhisa Nakayama
Seikagaku, 2012, Invited
Roles of the Arf family of small GTPases in membrane traffic
Analyses of interaction of FlP3 and FIP4 with Rab11 and ARFs and their roles in membrane traffic
Hiroshi Koga; Hye-Won Shin; Kazuhisa Nakayama
CELL STRUCTURE AND FUNCTION, Jun. 2005
Coordinated recruitment of Rab5, EEA1, type II inositol 5-phosphatase and type I inositol 4-phosphtase to peripheral ruffles in serum stimulated astrocytes.
M Hayashi; H Shin; S Lacas-Gervais; M Wenk; J Modregger; A Nystuen; WN Frankel; M Solimena; M Zerial; P De Camilli
MOLECULAR BIOLOGY OF THE CELL, Nov. 2004
An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway
H Shin; M Hayashi; S Christoforidis; S Lacas-Gervais; M Wenk; M Solimena; P De Camilli; M Zerial
MOLECULAR BIOLOGY OF THE CELL, Nov. 2004
BIG2, a guanine nucleotide exchange factor for ADP-ribosylation factors: Its localization to recycling endosomes and implication in the endosome integrity
K Nakayama; H Shin
MOLECULAR BIOLOGY OF THE CELL, Nov. 2004
BIG2 function on the endosomal compartment
Hye-Won Shin; Kazuhisa Nakayama
CELL STRUCTURE AND FUNCTION, May 2004
Vesicle fusion and tethering mechanism in Golgi complex
中村暢宏; 吉村信一郎; 申 惠媛
実験医学, 2003, Invited
タンパク質の輸送と細胞内局在、タンパク質がわかる
中山和久; 申惠媛; 中村暢宏
わかる実験医学シリーズ, 2003
Rab5-regulated phosphoinositides synthesis and turnover and its cellular function
H Shin; S Christoforidis; M Zerial
MOLECULAR BIOLOGY OF THE CELL, Nov. 2002
gamma-Adaptin interacts directly with Rabaptin-5 through its ear domain
K Nakayama; Y Shiba; H Takatsu; HW Shin
MOLECULAR BIOLOGY OF THE CELL, Dec. 2000
Presentations
Mechanism of cellular localization of lipid flippases
Hye-Won Shin
大阪大学タンパク質研究所セミナー生体膜上の生物化学, 05 Mar. 2021, Invited
Effect of temperature, ion and nucleotide on ATP8A1 and SERCA1a reaction mechanism
Distinct and redundant functions of BIG1 and BIG2 in the TGN and recycling endosomes
Ishizaki, R; Shin, H.-W; Nakayama, K
第10回細胞膜研究フォーラム, Feb. 2007
Dual Interaction of Arfophilins/Rab11-FIPs with ARFs and Rab11
Koga, H; Shin, H.-W; Nakayama, K
46th Annual Meeting of the American Society for Cell Biology, Dec. 2006
低分子量GTPase ARFRP1の機能解析
北村雅史; 申惠媛; 中山和久
日本分子生物学会2006フォーラム, Dec. 2006
細胞内小胞輸送におけるArfGAP1~ArfGAP3の機能解析
齋藤明奈; 申惠媛; 中山和久
日本分子生物学会2006フォーラム, Dec. 2006
FIP3、FIP4によるRab11とARFの機能のクロスト ーク
申 惠媛
日本分子生物学会2006フォーラム, Dec. 2006, Invited
Rab5-regulated phosphoinositide turnover in the endocytic pathway.
SHIN Hye-won
18th Annual Meeting of the Korean Society for Molecular and Cellular Biology, Oct. 2006, Invited
Dual Interaction of Arfophilins/Rab11-FIPs with ADP-ribosylation factor and Rab11
Koga, H; Shin, H.-W; Nakayama, K
20th IUBMB International Congress of Biochemistry and Molecular Biology, Jun. 2006
Regulation of membrane trafficking between the TGN and endosomes by ARF-GEFs
Nakayama, K; Shin, H.-W; Ishizaki, R
20th IUBMB International Congress of Biochemistry and Molecular Biology, Jun. 2006
AMY-1 is localized on the trans-Golgi network in association with brefeldin A-inhibited guanine nucleotide-exchange factor 2 (BIG2)
Ishizaki, R; Shin, H.-W; Iguchi-Ariga, S.M.M; Ariga, H; Nakayama, K
第9回国 際細胞膜研究フォーラム, Mar. 2006
Dual interaction of Arfophilins/Rab11-FIPs with ADP-ribosylation factor and Rab11
Koga, H; Shin, H.-W; Nakayama, K
第9回国際細胞膜研究フォーラム, Mar. 2006
Roles of ARFRP1 (ADP-Ribosylation Factor-Related Protein 1) in Post-Golgi Membrane Trafficking
Shin, H.-W; Kobayashi, H; Kitamura, M; Nakayama, K
45th Annual Meeting of the American Society for Cell Biology, Dec. 2005
細胞内膜輸送におけるBIGファミリータンパク質 の機能
申惠媛; 石崎玲; 中山和久
第27回生体膜と薬物の相互作用シンポジウム, Nov. 2005
BIG2, a Guanine Nucleotide Exchange Factor for ADP-Ribosylation Factors: Its Function at the Recycling Endosome
Shin, H.-W; Ishizaki, R; Nakayama, K
第78回日本生化学会大会, Oct. 2005
A New Method for Study of Post-Golgi Trafficking
Zhang, Q; Shin, H.-W; Nakayama, K
第78回日本生化学会大会, Oct. 2005
AMY-1 is localized on the trans-Golgi network in association with brefeldin A-inhibited guanine nucleotide-exchange factor 2 (BIG2)
Ishizaki, R; Shin, H.-W; Iguchi-Ariga, S.M.M; Ariga, H; Nakayama, K
第78回日本生化学会大会, Oct. 2005
BIG2, a guanine nucleotide exchange factor for ADP-ribosylation factors: Its Function at the recycling endosome.
申 惠媛
第78回日本生化学会大会, Oct. 2005, Invited
Role of ARFRP1 (ADP-ribosylation factor-related protein 1) in post-Golgi membrane traffic
Kitamura, M; Shin, H.-W; Kobayashi, H; Waguri, S; Uchiyama, Y; Nakayama, K
第58回日本細胞生物学会大会, Jun. 2005
Analyses of interaction of FIP3 and FIP4 with Rab11 and ARFs and their roles in membrane traffic
Koga, H; Shin, H.-W; Nakayama, K
第58回日本細胞生物学会大会, Jun. 2005
BIG2, a Guanine Nucleotide Exchange Factor for ADP-Ribosylation Factors: Its Localization to Recycling Endosomes and Implication in the Endosome Integrity
Nakayama, K; Shin, H.-W
44th Annual Meeting of the American Society for Cell Biology, Dec. 2004
An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway
Shin, H.-W; Hayashi, M; Christoforidis; S; Lacas-Gervais, S; Wenk, M; Solimena, M; De Camilli, P; Zerial, M
44th Annual Meeting of the American Society for Cell Biology, Dec. 2004
The subcellular localization and the role of ARF-related protein (ARF-RP)
Shin, H.-W; Kobayashi, H; Nakayama, K
第57回日本細胞生物学会大会, May 2004
BIG2 function on the endosomal compartment.
Shin, H.-W; Kobayashi, H; Nakayama, K
第57回日本細胞生物学会大会, May 2004
Rab5-regulated phosphoinositides synthesis and turnover and its cellular function
Shin, H.-W; Christoforidis, S; Zerial, M
42nd Annual Meeting of the American Society for Cell Biology, Dec. 2002
gamma-Adaptin interacts directly with Rabaptin-5 through its ear domain
Nakayama, K; Shiba, Y; Takatsu, H; Shin, H.-W
40th Annual meeting of American Society for Cell Biology, Dec. 2000
gamma-アダプチンとRabaptin5の相互作用の解析
芝陽子; 高津宏之; 申 惠媛; 中山和久
第73回日本生化学会大会, Oct. 2000
アダプター蛋白質複合体とCOP I複合体の形成は同様のサブユニット間相互作用により支配される
吉野佳織; 高津宏之; 二ツ森睦美; 吉田雄作; 申 惠媛; 中山和久
第73回日本生化学会大会, Oct. 2000
Self-association of Dnm1p/Vps1p-like protein (DVLP), a novel member of the dynamin GTPase family
Shin, H.-W
3rd Congress of the Asian-Pacific Organization for Cell Biology, Aug. 1998
新奇ダイナミン様GTP結合蛋白質の同定と細胞内局在
申 惠媛
第50回日本細胞生物学会大会, Sep. 1997
Regulation of activity and localization of phosphatidylserine flippase, ATP11C
https://www.asianscientist.com/2018/04/in-the-lab/atp10a-lipid-flip-membrane-deformation/, Apr. 2018, Internet
リン脂質の移動によって細胞膜が変形するメカニズムを解明
https://www.kyoto-u.ac.jp/ja/research-news/2018-03-30, Mar. 2018, Internet
Flipping lipids for cell transport-tubules
https://www.eurekalert.org/pub_releases/2018-03/ku-flf032818.php;https://phys.org/news/2018-03-flipping-lipids-cell-transport-tubules.html;https://www.sciencedaily.com/releases/2018/03/180329141014.htm, Mar. 2018, Internet
京大、細胞膜の脂質輸送の仕組みの一端を解明
https://www.nikkei.com/article/DGXLRSP463650_X11C17A1000000/?au=0, Nov. 2017, Internet
細胞膜の脂質輸送、セロトニンやヒスタミンの受容体の仕組みの一端を解明
https://www.kyoto-u.ac.jp/ja/research-news/2017-11-17-0, Nov. 2017, Internet
External funds: Kakenhi
Physiological roles of lipid asymmetry in biological membranes mediated by lipid flippases