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  • Li, HanbingZhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310014, Peoples R China.;Zhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China. (author)

Dual Function of PI(4,5)P2 in Insulin-Regulated Exocytic Trafficking of GLUT4 in Adipocytes

  • Article/chapterEnglish2020

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  • Elsevier BV,2020
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:uu-420524
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-420524URI
  • https://doi.org/10.1016/j.jmb.2020.06.019DOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Phosphoinositides are important signaling molecules involved in the regulation of vesicular trafficking. It has been implicated that phosphatidylinositol 4,5-bisphosphate [PI(4,5)P-2] is involved in insulin-regulated GLUT4 translocation in adipocytes. However, it remains unclear where and how PI(4,5)P-2 regulates discrete steps of GLUT4 vesicle translocation in adipocytes, especially on the exocytic arm of regulation. Here, we employed optogenetic tools to acutely control the PI(4,5)P-2 metabolism in living cells. By combination of TIRFM imaging, we were able to monitor the temporal-spatial-dependent PI(4,5)P-2 regulation on discrete steps of GLUT4 translocation in adipocytes. We found that the plasma membrane localized PI(4,5)P-2 is crucial for proper insulin signaling propagation and for insulin-stimulated GLUT4 vesicle translocation in 3T3-L1 adipocytes. Global depletion of PI(4,5)P-2 on the cell surface blunted insulin-stimulated Akt phosphorylation and abolished insulin effects in promotion of the docking and fusion of GLUT4 vesicle with the plasma membrane. Furthermore, by development of a novel optogenetic module to selectively modulate PI(4,5)P-2 levels on the GLUT4 vesicle docking site, we identified an important regulatory role of PI(4,5)P-2 in controlling of vesicle docking process. Local depletion of PI(4,5)P-2 at the vesicle docking site promoted GLUT4 vesicle undocking, diminished insulin-stimulated GLUT4 vesicle docking and fusion, but without perturbation of insulin signaling propagation in adipocytes. Our results provide strong evidence that cell surface PI(4,5)P-2 plays two distinct functions on regulation of the exocytic trafficking of GLUT4 in adipocytes. PI(4,5)P-2 not only regulates the proper activation of insulin signaling in general but also controls GLUT4 vesicle docking process at the vesicle-membrane contact sites.

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  • Shentu, PingZhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China. (author)
  • Xiao, MeiZhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310014, Peoples R China.;Zhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China. (author)
  • Zhao, XuqinZhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310014, Peoples R China.;Zhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China. (author)
  • Fan, JiannanZhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China. (author)
  • Liu, XuechunZhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China. (author)
  • Lin, YinyanZhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China. (author)
  • Wang, LeiZhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China. (author)
  • Li, HongZhejiang Univ, Affiliated Sir Run Run Shaw Hosp, Dept Endocrinol, Sch Med, Hangzhou 310016, Peoples R China. (author)
  • Guo, XiaogangZhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Cardiol, Hangzhou 310003, Peoples R China. (author)
  • Idevall Hagren, Olof,1980-Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)olide169 (author)
  • Xu, YingkeZhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China.;Zhejiang Univ, Affiliated Sir Run Run Shaw Hosp, Dept Endocrinol, Sch Med, Hangzhou 310016, Peoples R China. (author)
  • Zhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310014, Peoples R China.;Zhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China.Zhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China. (creator_code:org_t)

Related titles

  • In:Journal of Molecular Biology: Elsevier BV432:16, s. 4341-43570022-28361089-8638

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Li, Hanbing
Shentu, Ping
Xiao, Mei
Zhao, Xuqin
Fan, Jiannan
Liu, Xuechun
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Lin, Yinyan
Wang, Lei
Li, Hong
Guo, Xiaogang
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Xu, Yingke
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MEDICAL AND HEALTH SCIENCES
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Uppsala University

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