Lysosomal Trafficking, Antigen Presentation, and Microbial Killing Are Controlled by the Arf-like GTPase Arl8b
Antigen presentation and microbial killing are critical arms of host defense that depend upon cargo trafficking into lysosomes. Yet, the molecular regulators of traffic into lysosomes are only partly understood. Here, using a lysosome-dependent immunological screen of a trafficking shRNA library, we...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2013
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| Online Access: | http://hdl.handle.net/1721.1/82158 |
| _version_ | 1811085123971448832 |
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| author | Garg, Salil Sharma, Mahak Ung, Cindy Tuli, Amit Barral, Duarte C. Hava, David L. Veerapen, Natacha Besra, Gurdyal S. Hacohen, Nir Brenner, Michael B. |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Garg, Salil Sharma, Mahak Ung, Cindy Tuli, Amit Barral, Duarte C. Hava, David L. Veerapen, Natacha Besra, Gurdyal S. Hacohen, Nir Brenner, Michael B. |
| author_sort | Garg, Salil |
| collection | MIT |
| description | Antigen presentation and microbial killing are critical arms of host defense that depend upon cargo trafficking into lysosomes. Yet, the molecular regulators of traffic into lysosomes are only partly understood. Here, using a lysosome-dependent immunological screen of a trafficking shRNA library, we identified the Arf-like GTPase Arl8b as a critical regulator of cargo delivery to lysosomes. Homotypic fusion and vacuole protein sorting (HOPS) complex members were identified as effectors of Arl8b and were dependent on Arl8b for recruitment to lysosomes, suggesting that Arl8b-HOPS plays a general role in directing traffic to lysosomes. Moreover, the formation of CD1 antigen-presenting complexes in lysosomes, their delivery to the plasma membrane, and phagosome-lysosome fusion were all markedly impaired in Arl8b silenced cells resulting in corresponding defects in T cell activation and microbial killing. Together, these results define Arl8b as a key regulator of lysosomal cellular and immunological functions. |
| first_indexed | 2024-09-23T13:03:16Z |
| format | Article |
| id | mit-1721.1/82158 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:03:16Z |
| publishDate | 2013 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/821582022-09-28T11:45:44Z Lysosomal Trafficking, Antigen Presentation, and Microbial Killing Are Controlled by the Arf-like GTPase Arl8b Garg, Salil Sharma, Mahak Ung, Cindy Tuli, Amit Barral, Duarte C. Hava, David L. Veerapen, Natacha Besra, Gurdyal S. Hacohen, Nir Brenner, Michael B. Koch Institute for Integrative Cancer Research at MIT Garg, Salil Antigen presentation and microbial killing are critical arms of host defense that depend upon cargo trafficking into lysosomes. Yet, the molecular regulators of traffic into lysosomes are only partly understood. Here, using a lysosome-dependent immunological screen of a trafficking shRNA library, we identified the Arf-like GTPase Arl8b as a critical regulator of cargo delivery to lysosomes. Homotypic fusion and vacuole protein sorting (HOPS) complex members were identified as effectors of Arl8b and were dependent on Arl8b for recruitment to lysosomes, suggesting that Arl8b-HOPS plays a general role in directing traffic to lysosomes. Moreover, the formation of CD1 antigen-presenting complexes in lysosomes, their delivery to the plasma membrane, and phagosome-lysosome fusion were all markedly impaired in Arl8b silenced cells resulting in corresponding defects in T cell activation and microbial killing. Together, these results define Arl8b as a key regulator of lysosomal cellular and immunological functions. 2013-11-18T15:50:34Z 2013-11-18T15:50:34Z 2011-07 2011-02 Article http://purl.org/eprint/type/JournalArticle 10747613 http://hdl.handle.net/1721.1/82158 Garg, Salil, Mahak Sharma, Cindy Ung, Amit Tuli, Duarte C. Barral, David L. Hava, Natacha Veerapen, Gurdyal S. Besra, Nir Hacohen, and Michael B. Brenner. “Lysosomal Trafficking, Antigen Presentation, and Microbial Killing Are Controlled by the Arf-like GTPase Arl8b.” Immunity 35, no. 2 (August 2011): 182-193. © 2011 Elsevier Inc. en_US http://dx.doi.org/10.1016/j.immuni.2011.06.009 Immunity Article is available under a Creative Commons license. http://creativecommons.org/ application/pdf Elsevier PMC |
| spellingShingle | Garg, Salil Sharma, Mahak Ung, Cindy Tuli, Amit Barral, Duarte C. Hava, David L. Veerapen, Natacha Besra, Gurdyal S. Hacohen, Nir Brenner, Michael B. Lysosomal Trafficking, Antigen Presentation, and Microbial Killing Are Controlled by the Arf-like GTPase Arl8b |
| title | Lysosomal Trafficking, Antigen Presentation, and Microbial Killing Are Controlled by the Arf-like GTPase Arl8b |
| title_full | Lysosomal Trafficking, Antigen Presentation, and Microbial Killing Are Controlled by the Arf-like GTPase Arl8b |
| title_fullStr | Lysosomal Trafficking, Antigen Presentation, and Microbial Killing Are Controlled by the Arf-like GTPase Arl8b |
| title_full_unstemmed | Lysosomal Trafficking, Antigen Presentation, and Microbial Killing Are Controlled by the Arf-like GTPase Arl8b |
| title_short | Lysosomal Trafficking, Antigen Presentation, and Microbial Killing Are Controlled by the Arf-like GTPase Arl8b |
| title_sort | lysosomal trafficking antigen presentation and microbial killing are controlled by the arf like gtpase arl8b |
| url | http://hdl.handle.net/1721.1/82158 |
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