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Cytohesin 2/ARF6 regulates preadipocyte migration through the activation of ERK1/2

Jonathon C.B. Davies, Salman Tamaddon-Jahromi, Riaz Jannoo, Venkat Kanamarlapudi Orcid Logo

Biochemical Pharmacology, Volume: 92, Issue: 4, Pages: 651 - 660

Swansea University Author: Venkat Kanamarlapudi Orcid Logo

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DOI (Published version): 10.1016/j.bcp.2014.09.023

Abstract

Preadipocyte migration is vital for the development of adipose tissue, which plays a crucial role in lipid metabolism. ADP-ribosylation factor 6 (ARF6) small GTPase, which regulates membrane trafficking, is activated by GTP-exchange factors (GEFs) such as cytohesin 2. Cytohesin 2 and ARF6 have previ...

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Published in: Biochemical Pharmacology
Published: 2014
URI: https://cronfa.swan.ac.uk/Record/cronfa18768
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spelling 2019-10-11T18:18:51.2090432 v2 18768 2014-10-20 Cytohesin 2/ARF6 regulates preadipocyte migration through the activation of ERK1/2 63741801137148abfa4c00cd547dcdfa 0000-0002-8739-1483 Venkat Kanamarlapudi Venkat Kanamarlapudi true false 2014-10-20 BMS Preadipocyte migration is vital for the development of adipose tissue, which plays a crucial role in lipid metabolism. ADP-ribosylation factor 6 (ARF6) small GTPase, which regulates membrane trafficking, is activated by GTP-exchange factors (GEFs) such as cytohesin 2. Cytohesin 2 and ARF6 have previously been implicated in the regulation of 3T3-L1 preadipocyte migration. We investigated here the molecular mechanism underlying the cytohesin 2 and ARF6 mediated regulation of preadipocyte migration. Preadipocyte migration and the activation of ARF6 and ERK1/2 were studied by using a number of approaches, including pharmacological inhibitors, siRNA and the inhibitory peptides. The siRNA mediated down regulation of ARF6 and cytohesin 2 expression confirmed the requirement of both for migration of preadipocytes. Phosphatidylinositol 3-kinase (PI3K) and PI 4,5-bisphosphate (PIP2) have also found to be essential for the cytohesin 2/ARF6 induced preadipocyte migration. Pharmacological inhibition of the activation of ARF6, ERK1/2 or dynamin led to significant reduction in migration of 3T3-L1 preadipocytes. Furthermore, our study revealed the activation of ARF6 and ERK1/2 during migration of preadipocytes. In the migrating preadipocytes, ARF6 activation was inhibited with SecinH3 (cytohesin inhibitor) and LY294002 (PI3K inhibitor) whereas the ERK1/2 phosphorylation was inhibited with SecinH3, LY294002, PBP10 (a PIP2 sequester peptide) and PD98059 (MAPKK inhibitor). However, dynosore (dynamin inhibitor) had inhibited neither ARF6 activation nor ERK1/2 phosphorylation during preadipocyte migration. These results together suggest that cytohesin 2 activates ARF6 in a PI3K dependent manner and then the active ARF6 causes phosphorylation of ERK1/2 during preadipocyte migration. Journal Article Biochemical Pharmacology 92 4 651 660 Preadipocytes migration; ARF6; cytohesin 2; ERK; Dynamin 15 12 2014 2014-12-15 10.1016/j.bcp.2014.09.023 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2019-10-11T18:18:51.2090432 2014-10-20T11:53:54.0854824 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Jonathon C.B. Davies 1 Salman Tamaddon-Jahromi 2 Riaz Jannoo 3 Venkat Kanamarlapudi 0000-0002-8739-1483 4
title Cytohesin 2/ARF6 regulates preadipocyte migration through the activation of ERK1/2
spellingShingle Cytohesin 2/ARF6 regulates preadipocyte migration through the activation of ERK1/2
Venkat Kanamarlapudi
title_short Cytohesin 2/ARF6 regulates preadipocyte migration through the activation of ERK1/2
title_full Cytohesin 2/ARF6 regulates preadipocyte migration through the activation of ERK1/2
title_fullStr Cytohesin 2/ARF6 regulates preadipocyte migration through the activation of ERK1/2
title_full_unstemmed Cytohesin 2/ARF6 regulates preadipocyte migration through the activation of ERK1/2
title_sort Cytohesin 2/ARF6 regulates preadipocyte migration through the activation of ERK1/2
author_id_str_mv 63741801137148abfa4c00cd547dcdfa
author_id_fullname_str_mv 63741801137148abfa4c00cd547dcdfa_***_Venkat Kanamarlapudi
author Venkat Kanamarlapudi
author2 Jonathon C.B. Davies
Salman Tamaddon-Jahromi
Riaz Jannoo
Venkat Kanamarlapudi
format Journal article
container_title Biochemical Pharmacology
container_volume 92
container_issue 4
container_start_page 651
publishDate 2014
institution Swansea University
doi_str_mv 10.1016/j.bcp.2014.09.023
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 0
active_str 0
description Preadipocyte migration is vital for the development of adipose tissue, which plays a crucial role in lipid metabolism. ADP-ribosylation factor 6 (ARF6) small GTPase, which regulates membrane trafficking, is activated by GTP-exchange factors (GEFs) such as cytohesin 2. Cytohesin 2 and ARF6 have previously been implicated in the regulation of 3T3-L1 preadipocyte migration. We investigated here the molecular mechanism underlying the cytohesin 2 and ARF6 mediated regulation of preadipocyte migration. Preadipocyte migration and the activation of ARF6 and ERK1/2 were studied by using a number of approaches, including pharmacological inhibitors, siRNA and the inhibitory peptides. The siRNA mediated down regulation of ARF6 and cytohesin 2 expression confirmed the requirement of both for migration of preadipocytes. Phosphatidylinositol 3-kinase (PI3K) and PI 4,5-bisphosphate (PIP2) have also found to be essential for the cytohesin 2/ARF6 induced preadipocyte migration. Pharmacological inhibition of the activation of ARF6, ERK1/2 or dynamin led to significant reduction in migration of 3T3-L1 preadipocytes. Furthermore, our study revealed the activation of ARF6 and ERK1/2 during migration of preadipocytes. In the migrating preadipocytes, ARF6 activation was inhibited with SecinH3 (cytohesin inhibitor) and LY294002 (PI3K inhibitor) whereas the ERK1/2 phosphorylation was inhibited with SecinH3, LY294002, PBP10 (a PIP2 sequester peptide) and PD98059 (MAPKK inhibitor). However, dynosore (dynamin inhibitor) had inhibited neither ARF6 activation nor ERK1/2 phosphorylation during preadipocyte migration. These results together suggest that cytohesin 2 activates ARF6 in a PI3K dependent manner and then the active ARF6 causes phosphorylation of ERK1/2 during preadipocyte migration.
published_date 2014-12-15T03:22:03Z
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