HPIP and RUFY3 are noncanonical guanine nucleotide exchange factors of Rab5 to regulate endocytosis-coupled focal adhesion turnover
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
While the role of endocytosis in focal adhesion turnover-coupled cell migration has been established in addition to its conventional role in cellular functions, the molecular regulators and precise molecular mechanisms that underlie this process remain largely unknown. In this study, we report that proto-oncoprotein hematopoietic PBX-interacting protein (HPIP) localizes to focal adhesions as well as endosomal compartments along with RUN FYVE domain-containing protein 3 (RUFY3) and Rab5, an early endosomal protein. HPIP contains two coiled-coil domains (CC1 and CC2) that are necessary for its association with Rab5 and RUFY3 as CC domain double mutant, that is, mtHPIPΔCC1-2 failed to support it. Furthermore, we show that HPIP and RUFY3 activate Rab5 by serving as noncanonical guanine nucleotide exchange factors of Rab5. In support of this, either deletion of coiled-coil domains or silencing of HPIP or RUFY3 impairs Rab5 activation and Rab5-dependent cell migration. Mechanistic studies further revealed that loss of HPIP or RUFY3 expression severely impairs Rab5-mediated focal adhesion disassembly, FAK activation, fibronectin-associated-β1 integrin trafficking, and thus cell migration. Together, this study underscores the importance of HPIP and RUFY3 as noncanonical guanine nucleotide exchange factors of Rab5 and in integrin trafficking and focal adhesion turnover, which implicates in cell migration.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:299 |
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| Enthalten in: |
The Journal of biological chemistry - 299(2023), 11 vom: 20. Nov., Seite 105311 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Khumukcham, Saratchandra Singh [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 29.11.2023 Date Revised 06.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jbc.2023.105311 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM362913412 |
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| 100 | 1 | |a Khumukcham, Saratchandra Singh |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a HPIP and RUFY3 are noncanonical guanine nucleotide exchange factors of Rab5 to regulate endocytosis-coupled focal adhesion turnover |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 29.11.2023 | ||
| 500 | |a Date Revised 06.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a While the role of endocytosis in focal adhesion turnover-coupled cell migration has been established in addition to its conventional role in cellular functions, the molecular regulators and precise molecular mechanisms that underlie this process remain largely unknown. In this study, we report that proto-oncoprotein hematopoietic PBX-interacting protein (HPIP) localizes to focal adhesions as well as endosomal compartments along with RUN FYVE domain-containing protein 3 (RUFY3) and Rab5, an early endosomal protein. HPIP contains two coiled-coil domains (CC1 and CC2) that are necessary for its association with Rab5 and RUFY3 as CC domain double mutant, that is, mtHPIPΔCC1-2 failed to support it. Furthermore, we show that HPIP and RUFY3 activate Rab5 by serving as noncanonical guanine nucleotide exchange factors of Rab5. In support of this, either deletion of coiled-coil domains or silencing of HPIP or RUFY3 impairs Rab5 activation and Rab5-dependent cell migration. Mechanistic studies further revealed that loss of HPIP or RUFY3 expression severely impairs Rab5-mediated focal adhesion disassembly, FAK activation, fibronectin-associated-β1 integrin trafficking, and thus cell migration. Together, this study underscores the importance of HPIP and RUFY3 as noncanonical guanine nucleotide exchange factors of Rab5 and in integrin trafficking and focal adhesion turnover, which implicates in cell migration | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a HPIP/PBXIP1 | |
| 650 | 4 | |a RUFY3 | |
| 650 | 4 | |a Rab5 | |
| 650 | 4 | |a cell migration | |
| 650 | 4 | |a endocytosis | |
| 650 | 4 | |a focal adhesion kinase | |
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| 650 | 7 | |a HCFC1R1 protein, human |2 NLM | |
| 650 | 7 | |a RUFY3 protein, human |2 NLM | |
| 650 | 7 | |a RAB5C protein, human |2 NLM | |
| 650 | 7 | |a EC 3.6.1.- |2 NLM | |
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| 700 | 1 | |a Bugide, Suresh |e verfasserin |4 aut | |
| 700 | 1 | |a Dwivedi, Anju |e verfasserin |4 aut | |
| 700 | 1 | |a Kumari, Anita |e verfasserin |4 aut | |
| 700 | 1 | |a Kesavan, P S |e verfasserin |4 aut | |
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| 700 | 1 | |a Nagarajaram, Hampapathalu A |e verfasserin |4 aut | |
| 700 | 1 | |a Mazumder, Aprotim |e verfasserin |4 aut | |
| 700 | 1 | |a Manavathi, Bramanandam |e verfasserin |4 aut | |
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