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Dual Function of PI...
Dual Function of PI(4,5)P2 in Insulin-Regulated Exocytic Trafficking of GLUT4 in Adipocytes
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- Li, Hanbing (författare)
- 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.
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- Shentu, Ping (författare)
- Zhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China.
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- Xiao, Mei (författare)
- 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.
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- Zhao, Xuqin (författare)
- 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.
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- Fan, Jiannan (författare)
- Zhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China.
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- Liu, Xuechun (författare)
- Zhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China.
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- Lin, Yinyan (författare)
- Zhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China.
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- Wang, Lei (författare)
- Zhejiang Univ, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Minist Educ, Dept Biomed Engn,Key Lab Biomed Engn, Hangzhou 310027, Peoples R China.
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- Li, Hong (författare)
- Zhejiang Univ, Affiliated Sir Run Run Shaw Hosp, Dept Endocrinol, Sch Med, Hangzhou 310016, Peoples R China.
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- Guo, Xiaogang (författare)
- Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Cardiol, Hangzhou 310003, Peoples R China.
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- Idevall Hagren, Olof, 1980- (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Xu, Yingke (författare)
- 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, Affiliated Sir Run Run Shaw Hosp, Dept Endocrinol, Sch Med, Hangzhou 310016, Peoples R China.
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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)
- Elsevier BV, 2020
- 2020
- Engelska.
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 432:16, s. 4341-4357
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- optogenetics
- phosphoinositide
- GLUT4
- TIRFM
- exocytosis
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Li, Hanbing
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Shentu, Ping
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Xiao, Mei
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Zhao, Xuqin
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Fan, Jiannan
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Liu, Xuechun
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visa fler...
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Lin, Yinyan
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Wang, Lei
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Li, Hong
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Guo, Xiaogang
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Idevall Hagren, ...
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Xu, Yingke
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Uppsala universitet