FY2023 Annual Report

Membranology Unit
Assistant Professor Keiko Kono

Abstract

In FY2023, Kono Unit had a harvest time after six years of continuous efforts. The team published two original papers and one review article. Two Ph.D. students successfully defended their thesis. Two members won the best poster award at the conference. Three members moved on to the next stage of their scientific journey.

 

1. Staff

  • Dr. Yohsuke Moriyama, Science and Technology Associate

  • Dr. Shinju Sugiyama, Postdoc

  • Dr. Nurhanani Binti Razali, Postdoc

  • Mr. Hunter Barbee, Ph.D. Student (Ph.D. in October 2023)

  • Ms. Yatzu Chiu, Ph.D. Student

  • Mr. Kojiro Suda, Ph.D. Student (Ph.D. in March 2024)

  • Mr. Jan Grašič, Ph.D. Student

  • Mr. Yuta Yamazaki, Ph.D. Student

  • Ms. Kamila Krystyna Kozik, Ph.D. Student

  • Ms. Hiyori Mori, Intern student at Keio University Medical Department

  • Ms. Hitomi Ohtaki, Research Unit Administrator

Co-supervision

  • Ms. Aisulu Maipas, Ph.D. Student@ Yamamoto Unit

  • Ms. Sara Abdelaal, Ph.D. Student@ Terenzio Unit  (Ph.D. in February 2024)

  • Mr. Masato Hirota, Ph.D. Student@ Ishikawa Unit

2. Collaborations

2.1  Plasma membrane damage response in laboratory yeast and industrial yeast for brewing

  • Type of collaboration: Joint research
  • Researchers:
    • Dr. Nozomu Kamada, SUNTORY
    • Dr. Atsushi Fujita, SUNTORY

2.2 Mechanisms, consequences, and prevention of plasma membrane damage-dependent cellular senescence

  • Type of collaboration: Joint research
  • Researchers:
    • Dr. Takayuki Izumo, SUNTORY Wellness
    • Dr. Daisuke Takemoto, SUNTORY Wellness
    • Ms. Yuki Nakamura, SUNTORY Wellness
    • Mr. Takakiyo Naganawa, SUNTORY Wellness

2.3 The mechanism underlying ethanol-dependent misdirected cell division and cancer development

  • Type of collaboration: Joint research
  • Researchers:
    • Prof. Junichi Ikenouchi, Kyushu University
    • Dr. Atsushi Matsumoto Kyushu University

2.4 Biomarkers for healthy aging

  • Type of collaboration: Joint research
  • Researchers:
    • Prof. Olle Melander, Lund University
    • Prof. Thomas Svensson, University of Tokyo
    • Prof. Akiko Kishi, University of Tokyo

3. Activities and Findings

3.1 Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts

Plasma membrane damage occurs in all cell types due to environmental perturbation and cell-autonomous activities. However, cellular outcomes of PMD remain largely unknown except for recovery or death. We showed that 1) plasma membrane damage induces cellular senescence, and 2) the gene expression profiles of plasma membrane damage-dependent senescent cells are analogous to that of senescent cells near cutaneous wounds in the human body. 

 

 

3.2  Exocytic plasma membrane flows remodel endoplasmic reticulum–plasma membrane tethering for septin collar assembly

Endoplasmic reticulum (ER)–plasma membrane (PM) tethering is crucial for the non-vesicular lipid transport between the ER membrane and the PM. However, the PM-associated ER can impede the PM binding of cytoskeletons and other organelles. It is poorly understood how the competition between the ER and cytoskeletons/organelles on the PM is resolved. Here, we show that, upon septin collar assembly, ER-PM tethering proteins are excluded from the yeast bud sites, and the PM-associated ER is locally detached from the PM. Our results suggest that PM flows by polarized exocytosis extrude PM proteins, including ER-PM tethering proteins, from the bud sites. When the reorganization of the ER-PM tethering was inhibited by exocytosis repression, septin localization was restricted to the PM sites poor in ER-PM tethering proteins. This study proposes machinery reconciling ER-septin competition on the PM, providing mechanistic insights into the spatial organization of PM-associated organelles and cytoskeletons.

4. Publications

4.1 Journals

  1. Suda K#, Moriyama Y#, Razali N#, Chiu Y, Masukagami Y, Nishimura K, Barbee H, Takase H, Sugiyama S, Yamazaki Y, Sato Y, Higashiyama T, Johmura Y, Nakanishi M, and Kono K*. Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts. (2024) Nature Aging. DOI: https://doi.org/10.1038/s43587-024-00575-6 Featured on the cover. Introduced in News and Views and Spotlight. 
  2. Sugiyama S*, and Kono K*. Exocytic plasma membrane flows remodel endoplasmic reticulum-plasma membrane tethering for septin collar assembly. (2024) Science Advances. March 13th online, ol 10, Issue 11 DOI: 10.1126/sciadv.adj1512
  3. El-Agamy SE, Guillaud L, Kono K, Wu Y, Terenzio M*. FMRP Long-Range Transport and Degradation Are Mediated by Dynlrb1 in Sensory Neurons. (2023) Mol. Cell Proteomics. 22:100653.
  4. Sugiyama S, Suda K, and Kono K*. “Cytoplasmic zoning by protein phase transition after membrane permeabilization” Journal of Biochemistry. 2023 Nov 16:mvad094. doi: 10.1093/jb/mvad094. 

4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations

International

  1. Kono K. “Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts” (2024 Jan) A3 Foresight program, Cellular Senescence: from Pathophysiology to Treatment. Osaka. 
  2. Kono K. “Plasma Membrane Damage Induces Cellular Senescence” (2023 Dec) MIT, Boston, USA. Seminar.
  3. Kono K. "Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts" (2023 Dec), Cell Bio 2023-An ASCB|EMBO Meeting, Boston.
  4. Sugiyama S and Kono K. “Exocytic plasma membrane flows remodel endoplasmic reticulum-plasma membrane tethering for septin collar assembly” (2023 Oct) Cold Spring Harbor Asia conference on Yeast and Life Sciences, Shimane. 
  5. Kono K. "How do our cells age?" (2024 Mar) RIKEN iTHEMS x OIST, OIST, Okinawa.
  6. Chiu Y, Moriyama Y and Kono K."Time-resolved miRNA-mRNA Integrated Analysis Revealed the miRNA-mRNA Networks underlying the Cellular Senescence in Normal Human  Fibroblasts" (2023 May), RNA2023, Singapore.
  7. Grašič J, Suda K, Razali N, Taoufiq Z, Chiu Y, Moriyama Y, KonoK. "Time-resolved proteomic profiling of plasma membrane damage-dependent senescence reveals upregulation of wound healing response at the early stage of senescence" (2023 Oct), ICSA2023, Minnesota.
  8. Yamazaki Y and Kono K. "Time-resolved dynamics of plasma membrane repair proteins" (2024 Feb), 67th Biophysical Society Annual Meeting, San Diego.
  9. Suda Y and Kono K. "Plasma membrane damage induces cellular senescence via mitochondrial Ca2+ accumulation" (2024 Jan) A3 Foresight program, Cellular Senescence: from Pathophysiology to Treatment. Osaka. Best Poster Prize
  10. Razali N, Moriyama Y, Chiu Y, Suda K, and Kono K. "Time-resolved transcriptomic profiling of senescence-associated secretory phenotype (SASP) in multiple senescent cell subtypes" (2024 Jan) A3 Foresight program, Cellular Senescence: from Pathophysiology to Treatment. Osaka.
  11. Kozik K and Kono K. "PAK1-Dependent Macropinocytosis is Upregulated in Senescent Cells"  (2024 Jan) A3 Foresight program, Cellular Senescence: from Pathophysiology to Treatment. Osaka.
  12. Grašič J, Suda K, Razali N, Taoufiq Z, Chiu Y, Moriyama Y, Kono K. "Time-resolved proteomic profiling of plasma membrane damage-dependent senescence reveals upregulation of wound healing response at the early stage of senescence"  (2024 Jan) A3 Foresight program, Cellular Senescence: from Pathophysiology to Treatment. Osaka.

Domestic

  1. Kono K. “Ca2+-mediated ER-mitochondria crosstalk during plasma membrane damage-dependent senescence” (2024 Mar), The 101th Annual Meeting of the Physiological Society of Japan. Kokura, Symposium
  2. Kono K. “Plasma membrane damage-dependent cellular senescence is mediated by mitochondrial Ca2+ accumulation” (2023 Nov), The 96th Annual Conference of Japanese Biochemical Society. Fukuoka, Symposium
  3. Kono K. “Plasma membrane damage-dependent cellular senescence is mediated by mitochondrial Ca2+ accumulation” (2023 Nov) 1st OIST RIKEN Meeting. OIST, Okinawa
  4. Kono K. “Alteration of cytosolic zoning after plasma membrane damage” (2023 July), The 23rd Annual Meeting of the Protein Science Society of Japan. Nagoya. Workshop
  5. Chiu Y, Moriyama Y and Kono K."Time-resolved miRNA-mRNA Integrated Analysis Revealed the miRNA-mRNA Networks underlying the Cellular Senescence in Normal Human  Fibroblasts" (2023 July), RNA2023 Japan, Okinawa.
  6. Razali N, Moriyama Y, Chiu Y, Suda K, Kono K. "Time-resolved transcriptomic profiling of senescence-associated secretory phenotype (SASP) in multiple
    senescent cell subtypes" (2023 Nov),  The 96th Annual Conference of Japanese Biochemical Society. Fukuoka

 

5. Intellectual Property Rights and Other Specific Achievements

Nothing to report

6. Meetings and Events

6.1 Extracellular vesicles from paclitaxel-induced senescent TNBC elicit paracrine anti-tumour effects in a STING-dependent manner

  • Date: October 30, 2023
  • Venue: OIST Campus C700, Lab3
  • Speaker: Dr. Crasta Karen Carmelina (National University of Singapore)

6.2 The role of non coding RNA in genome stability in cancer and aging

  • Date: November 16, 2023
  • Venue: OIST Campus B503, Lab1
  • Speaker: Dr. Fabrizio d’Adda di Fagagna (IFOM ETS – The AIRC Institute of Molecular Oncology)

6.3 How are tight junctions different from other cell adhesion structures?

  • Date: March 1, 2024
  • Venue: OIST Campus D23, Lab5
  • Speaker: Dr. Junichi Ikenouchi (Kyushu University)

6.4 Regulation and functions of epithelial-cell specific lipid composition.

  • Date: March 1, 2024
  • Venue: OIST Campus D23, Lab5
  • Speaker: Dr. Atsushi Matsumoto (Kyushu University)

6.5 OIST x iTHEMS workshop series 

  • Date: March 4-6, 2024
  • Venue: OIST Campus D23, Lab5
  • Scientific Organizers: Dr. Shigehiro Nagataki (OIST/RIKEN, iTHEMS), Dr. Evan Economo (OIST), Dr. Keiko Kono (OIST)

7. Other

Nothing to report.