The TBC/RabGAP Armus Coordinates Rac1 and Rab7 Functions during Autophagy
Autophagy is an evolutionarily conserved process that enables catabolic and degradative pathways. These pathways commonly depend on vesicular transport controlled by Rabs, small GTPases inactivated by TBC/RabGAPs. The Rac1 effector TBC/RabGAP Armus (TBC1D2A) is known to inhibit Rab7, a key regulator...
| 主要な著者: | , , , , , , , , , , , , |
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| フォーマット: | Journal article |
| 出版事項: |
Elsevier
2013
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| _version_ | 1826294895014313984 |
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| author | Carroll, B Mohd-Naim, N Maximiano, F Frasa, M McCormack, J Finelli, M Thoresen, S Perdios, L Daigaku, R Francis, R Futter, C Dikic, I Braga, V |
| author_facet | Carroll, B Mohd-Naim, N Maximiano, F Frasa, M McCormack, J Finelli, M Thoresen, S Perdios, L Daigaku, R Francis, R Futter, C Dikic, I Braga, V |
| author_sort | Carroll, B |
| collection | OXFORD |
| description | Autophagy is an evolutionarily conserved process that enables catabolic and degradative pathways. These pathways commonly depend on vesicular transport controlled by Rabs, small GTPases inactivated by TBC/RabGAPs. The Rac1 effector TBC/RabGAP Armus (TBC1D2A) is known to inhibit Rab7, a key regulator of lysosomal function. However, the precise coordination of signaling and intracellular trafficking that regulates autophagy is poorly understood. We find that overexpression of Armus induces the accumulation of enlarged autophagosomes, while Armus depletion significantly delays autophagic flux. Upon starvation-induced autophagy, Rab7 is transiently activated. This spatiotemporal regulation of Rab7 guanosine triphosphate/guanosine diphosphate cycling occurs by Armus recruitment to autophagosomes via interaction with LC3, a core autophagy regulator. Interestingly, autophagy potently inactivates Rac1. Active Rac1 competes with LC3 for interaction with Armus and thus prevents its appropriate recruitment to autophagosomes. The precise coordination between Rac1 and Rab7 activities during starvation suggests that Armus integrates autophagy with signaling and endocytic trafficking. |
| first_indexed | 2024-03-07T03:52:44Z |
| format | Journal article |
| id | oxford-uuid:c1d6a0fc-2daf-446e-a734-6051b16c8ed8 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T03:52:44Z |
| publishDate | 2013 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:c1d6a0fc-2daf-446e-a734-6051b16c8ed82022-03-27T06:04:27ZThe TBC/RabGAP Armus Coordinates Rac1 and Rab7 Functions during AutophagyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c1d6a0fc-2daf-446e-a734-6051b16c8ed8Symplectic Elements at OxfordElsevier2013Carroll, BMohd-Naim, NMaximiano, FFrasa, MMcCormack, JFinelli, MThoresen, SPerdios, LDaigaku, RFrancis, RFutter, CDikic, IBraga, VAutophagy is an evolutionarily conserved process that enables catabolic and degradative pathways. These pathways commonly depend on vesicular transport controlled by Rabs, small GTPases inactivated by TBC/RabGAPs. The Rac1 effector TBC/RabGAP Armus (TBC1D2A) is known to inhibit Rab7, a key regulator of lysosomal function. However, the precise coordination of signaling and intracellular trafficking that regulates autophagy is poorly understood. We find that overexpression of Armus induces the accumulation of enlarged autophagosomes, while Armus depletion significantly delays autophagic flux. Upon starvation-induced autophagy, Rab7 is transiently activated. This spatiotemporal regulation of Rab7 guanosine triphosphate/guanosine diphosphate cycling occurs by Armus recruitment to autophagosomes via interaction with LC3, a core autophagy regulator. Interestingly, autophagy potently inactivates Rac1. Active Rac1 competes with LC3 for interaction with Armus and thus prevents its appropriate recruitment to autophagosomes. The precise coordination between Rac1 and Rab7 activities during starvation suggests that Armus integrates autophagy with signaling and endocytic trafficking. |
| spellingShingle | Carroll, B Mohd-Naim, N Maximiano, F Frasa, M McCormack, J Finelli, M Thoresen, S Perdios, L Daigaku, R Francis, R Futter, C Dikic, I Braga, V The TBC/RabGAP Armus Coordinates Rac1 and Rab7 Functions during Autophagy |
| title | The TBC/RabGAP Armus Coordinates Rac1 and Rab7 Functions during Autophagy |
| title_full | The TBC/RabGAP Armus Coordinates Rac1 and Rab7 Functions during Autophagy |
| title_fullStr | The TBC/RabGAP Armus Coordinates Rac1 and Rab7 Functions during Autophagy |
| title_full_unstemmed | The TBC/RabGAP Armus Coordinates Rac1 and Rab7 Functions during Autophagy |
| title_short | The TBC/RabGAP Armus Coordinates Rac1 and Rab7 Functions during Autophagy |
| title_sort | tbc rabgap armus coordinates rac1 and rab7 functions during autophagy |
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