Yongsoo Park Lab

NeuroBiology

RIBOMONE - Yongsoo Park Lab

RESEARCH

<p>1. We study microRNA exocytosis by LDCV fusion. Our research and data are opening the new field and concept that microRNA can be a novel neuromodulator, which is stored inside the vesicle and released together with classical neurotransmitters by vesicle fusion, thereby contributing to cell-to-cell communication.</p>
<p>2. My group aims to investigate the molecular mechanisms of vesicle fusion by combining interdisciplinary techniques that include cell biological, biophysical, and biochemical tools.</p>
<p>3. We focus on neuronal differentiation of human induced pluripotent stem cells (hiPSC) as a disease model of autism and neurodegenerative disorders. hiPSCs-derived neurons can be used for personalized medicine to cure autism and neurodegenerative disorders.</p>

1. We study microRNA exocytosis by LDCV fusion. Our research and data are opening the new field and concept that microRNA can be a novel neuromodulator, which is stored inside the vesicle and released together with classical neurotransmitters by vesicle fusion, thereby contributing to cell-to-cell communication.

2. My group aims to investigate the molecular mechanisms of vesicle fusion by combining interdisciplinary techniques that include cell biological, biophysical, and biochemical tools.

3. We focus on neuronal differentiation of human induced pluripotent stem cells (hiPSC) as a disease model of autism and neurodegenerative disorders. hiPSCs-derived neurons can be used for personalized medicine to cure autism and neurodegenerative disorders.

<p>Although microRNA (miRNA) regulates gene expression inside the cell where they are transcribed, extracellular miRNA has been recently discovered outside the cells, proposing that miRNA might be released to participate in cell-to-cell communication (Front Endocrinol. 2017).</p>
<p>My group first reported the active exocytosis of miRNAs independently of exosomes in response to neuronal stimulation.</p>
<p>We propose a new function of non-coding RNAs named (‘ribomone’ = ribonucleotide + hormone), and suggest that miRNAs may function as hormones; i.e., miRNA is stored in vesicles and released by vesicle fusion in response to stimulation, thereby contributing to cell-to-cell communication.</p>

Although microRNA (miRNA) regulates gene expression inside the cell where they are transcribed, extracellular miRNA has been recently discovered outside the cells, proposing that miRNA might be released to participate in cell-to-cell communication (Front Endocrinol. 2017).

My group first reported the active exocytosis of miRNAs independently of exosomes in response to neuronal stimulation.

We propose a new function of non-coding RNAs named (‘ribomone’ = ribonucleotide + hormone), and suggest that miRNAs may function as hormones; i.e., miRNA is stored in vesicles and released by vesicle fusion in response to stimulation, thereby contributing to cell-to-cell communication.

Array

Vesicles in neurons and neuroendocrine cells store neurotransmitters and peptide hormones, which are released by vesicle fusion in response to Ca2+‐evoking stimuli. Synaptotagmin‐1 (Syt1), a Ca2+ sensor, mediates ultrafast exocytosis in neurons and neuroendocrine cells.

The molecular mechanisms by which Syt1 triggers vesicle fusion remain controversial; six molecular models of Syt1 are summarized above (FEBS Lett. 2018).

We are investigating to unveil the novel mechanisms of vesicle fusion using synthetic neurotransmission that reconstitutes the vesicle fusion process with purified native vesicles, i.e., synaptic vesicles and large dense-core vesicles (LDCVs). Synthetic neurotransmission allows us to directly explore the mechanisms of vesicle fusion.

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Use of neuronal differentiation of induced pluripotent stem cells (iPSC) as a disease model of autism and neurodegenerative disorders.

Some specific questions I wish to address are:

i) to identify functionally active iPSC-derived neurons using calcium imaging and patch clamp techniques.

ii) to examine that the mutation of ion channels related to autism is corrected by CRISPR-Cas9 and edited ion channels recover the ionic current in iPSC neurons as an autism model.

Team

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Yongsoo Park, Ph.D.

Scientist / Assistant Professor

Member, EMBO Young Investigator Programme (YIP) as an EMBO Installation Grantee, 2016-2019.

LinkedIn / ResearchGate Google Scholar


 

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Kyung Chul Shin, Ph.D.

Postdoctoral Fellow


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Yelda Birinci, Ph.D.

Postdoctoral Fellow


 

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Houda Yasmine Ali Moussa

Research Associate


 

Alumni

Alican Gümürdü Graduate Student

Obadah Al Bahra Graduate Student

Ramazan Yildiz Graduate Student

Selected Publications

#, Corresponding author

Full lists in PubMed.

  1. Ali Moussa HY, Shin KC, Ponraj J, Park SH, Lee OS, Mansour S, Park Y#. PIP2 Is an electrostatic Catalyst for Vesicle Fusion by Lowering the Hydration Energy: Arresting Vesicle Fusion by Masking PIP2. ACS Nano. 2024, 18, 20, 12737-12748. Highlighted as a supplementary Cover.
  2. Shin KC, Ali G, Ali Moussa HY, Gupta V, de la Fuente A, Kim HG, Stanton LW, Park Y#. Deletion of TRPC6, an autism risk gene, induces hyperexcitability in cortical neurons derived from human pluripotent stem cells. Mol Neurobiol. 2023 Aug 8.
  3. Ali Moussa HY, Shin KC, Ponraj J, Kim SJ, Ryu JK, Mansour S, Park Y#. Requirement of cholesterol for calcium-dependent vesicle fusion by strengthening synaptotagmin-1-induced membrane bending. Adv Sci. 2023 May;10(15):e2206823. Highlighted as a Frontispiece.
  4. Ali Moussa HY, Park Y#. Electrostatic regulation of the cis- and trans-membrane interactions of synaptotagmin-1. Sci Rep. 2022 Dec 27;12(1):22407.
  5. Ali Moussa HY, Manaph N, Ali G, Maacha S, Shin KC, Ltaief SM, Gupta V, Tong Y, Ponraj J, Salloum-Asfar S, Mansour S, Al-Shaban FA, Kim HG, Stanton LW, Grivel JC, Abdulla SA, Al-Shammari AR#, Park Y#. Single extracellular vesicle analysis using flow cytometry for neurological disorder biomarkers. Front Integr Neurosci. 2022 May 17;16:879832.
  6. Birinci Y, Preobraschenski J, Ganzella M, Jahn R, Park Y#. Isolation of large dense-core vesicles from bovine adrenal medulla for functional studies. Sci Rep. 2020 May 5;10(1):7540.
  7. Park Y# and Ryu JK#. Models of synaptotagmin-1 to trigger Ca2+-dependent vesicle fusion. FEBS Lett. 2018 Nov;592(21):3480-3492.
  8. Park Y#, MicroRNA exocytosis by vesicle fusion in neuroendocrine cells. Front Endocrinol. 2017 Dec 22;8:355.
  9. Gümürdü A, Yildiz R, Eren E, Karakülah G, Ünver T, GENÇ Ş, and Park Y#. MicroRNA exocytosis by large dense-core vesicle fusion. Sci Rep. 2017 Mar 30;7:45661.
  10. Park Y, Seo JB, Fraind A, Pérez-Lara A, Yavuz H, Han K, Jung SR, Kattan I, Walla PJ, Choi MY, Cafiso DS, Koh DS, Jahn R. Synaptotagmin-1 binds to PIP2-containing membrane but not to SNAREs at physiological ionic strength. Nature Struct Mol Biol. 2015 Oct;22(10):815-823.
  11. Park Y, Vennekate W, Yavuz H, Preobraschenski J, Hernandez JM, Riedel D, Walla PJ, Jahn R. α-SNAP interferes with the zippering of the SNARE membrane fusion machinery. J Biol Chem. 2014 Jun 6;289(23):16326-16335.
  12. Park Y, Hernandez J. M, van den Bogaart G, Ahmed S, Holt M, Riedel D, and Jahn R. Controlling synaptotagmin activity by electrostatic screening. Nature Struct Mol Biol. 2012 Oct;19(10):991-997.
  13. Park Y and Kim KT. Dominant role of lipid rafts L-type calcium channel in activity-dependent potentiation of large dense-core vesicle exocytosis. J Neurochem. 2009 Jul;110(2):520-529.
  14. Park Y and Kim KT. Short-term plasticity of small synaptic vesicle (SSV) and large dense-core vesicle (LDCV) exocytosis. Cell Signal. 2009 Oct;21(10):1465-70.
  15. Park YS, Choi YH, Park CH, Kim KT. Non-genomic glucocorticoid effects on activity-dependent potentiation of catecholamine release in chromaffin cells. Endocrinology. 2008 Oct;149(10):4921-7.
  16. Park YS, Hur EM, Choi BH, Kwak E, Jun DJ, Park SJ, Kim KT. Involvement of protein kinase C-epsilon in activity-dependent potentiation of large dense-core vesicle exocytosis in chromaffin cells. J Neurosci. 2006 Aug 30;26(35): 8999-9005.
  17. (Cover article) Park YS, Jun DJ, Hur EM, Lee SK, Suh BS, Kim KT. Activity-dependent potentiation of large dense-core vesicle release modulated by mitogen-activated protein kinase(MAPK)/ERK signaling. Endocrinology. 2006 Mar;147(3):1349-56.

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Address

Qatar Biomedical Research Institute (QBRI),
College of Health & Life Sciences (CHLS),
Hamad Bin Khalifa University (HBKU),
Education City, Doha, Qatar

PHONE & E-MAIL

Email: ypark@hbku.edu.qa