Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors.
A key requirement for Rab function in membrane trafficking is site-specific activation by GDP-GTP exchange factors (GEFs), but the majority of the 63 human Rabs have no known GEF. We have performed a systematic characterization of the 17 human DENN domain proteins and demonstrated that they are spec...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2010
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| _version_ | 1826272732076048384 |
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| author | Yoshimura, S Gerondopoulos, A Linford, A Rigden, D Barr, F |
| author_facet | Yoshimura, S Gerondopoulos, A Linford, A Rigden, D Barr, F |
| author_sort | Yoshimura, S |
| collection | OXFORD |
| description | A key requirement for Rab function in membrane trafficking is site-specific activation by GDP-GTP exchange factors (GEFs), but the majority of the 63 human Rabs have no known GEF. We have performed a systematic characterization of the 17 human DENN domain proteins and demonstrated that they are specific GEFs for 10 Rabs. DENND1A/1B localize to clathrin patches at the plasma membrane and activate Rab35 in an endocytic pathway trafficking Shiga toxin to the trans-Golgi network. DENND2 GEFs target to actin filaments and control Rab9-dependent trafficking of mannose-6-phosphate receptor to lysosomes. DENND4 GEFs target to a tubular membrane compartment adjacent to the Golgi, where they activate Rab10, which suggests a function in basolateral polarized sorting in epithelial cells that compliments the non-DENN GEF Sec2 acting on Rab8 in apical sorting. DENND1C, DENND3, DENND5A/5B, MTMR5/13, and MADD activate Rab13, Rab12, Rab39, Rab28, and Rab27A/27B, respectively. Together, these findings provide a basis for future studies on Rab regulation and function. |
| first_indexed | 2024-03-06T22:17:14Z |
| format | Journal article |
| id | oxford-uuid:53c9c692-d6ae-4b08-89fe-bb0908162333 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:17:14Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:53c9c692-d6ae-4b08-89fe-bb09081623332022-03-26T16:33:55ZFamily-wide characterization of the DENN domain Rab GDP-GTP exchange factors.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:53c9c692-d6ae-4b08-89fe-bb0908162333EnglishSymplectic Elements at Oxford2010Yoshimura, SGerondopoulos, ALinford, ARigden, DBarr, FA key requirement for Rab function in membrane trafficking is site-specific activation by GDP-GTP exchange factors (GEFs), but the majority of the 63 human Rabs have no known GEF. We have performed a systematic characterization of the 17 human DENN domain proteins and demonstrated that they are specific GEFs for 10 Rabs. DENND1A/1B localize to clathrin patches at the plasma membrane and activate Rab35 in an endocytic pathway trafficking Shiga toxin to the trans-Golgi network. DENND2 GEFs target to actin filaments and control Rab9-dependent trafficking of mannose-6-phosphate receptor to lysosomes. DENND4 GEFs target to a tubular membrane compartment adjacent to the Golgi, where they activate Rab10, which suggests a function in basolateral polarized sorting in epithelial cells that compliments the non-DENN GEF Sec2 acting on Rab8 in apical sorting. DENND1C, DENND3, DENND5A/5B, MTMR5/13, and MADD activate Rab13, Rab12, Rab39, Rab28, and Rab27A/27B, respectively. Together, these findings provide a basis for future studies on Rab regulation and function. |
| spellingShingle | Yoshimura, S Gerondopoulos, A Linford, A Rigden, D Barr, F Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors. |
| title | Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors. |
| title_full | Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors. |
| title_fullStr | Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors. |
| title_full_unstemmed | Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors. |
| title_short | Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors. |
| title_sort | family wide characterization of the denn domain rab gdp gtp exchange factors |
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