| Added by | mollevi |
|---|---|
| Last modified by | alainmange |
| Group name | PlateformePP2I |
| Item Type | Journal Article |
| Title | Cyclophilin A enables specific HIV-1 Tat palmitoylation and accumulation in uninfected cells |
| Creator | Chopard et al. |
| Author | Christophe Chopard |
| Author | Phuoc Bao Viet Tong |
| Author | Petra Tóth |
| Author | Malvina Schatz |
| Author | Hocine Yezid |
| Author | Solène Debaisieux |
| Author | Clément Mettling |
| Author | Antoine Gross |
| Author | Martine Pugnière |
| Author | Annie Tu |
| Author | Jean-Marc Strub |
| Author | Jean-Michel Mesnard |
| Author | Nicolas Vitale |
| Author | Bruno Beaumelle |
| Abstract | Most HIV-1 Tat is unconventionally secreted by infected cells following Tat interaction with phosphatidylinositol (4,5) bisphosphate (PI(4,5)P2) at the plasma membrane. Extracellular Tat is endocytosed by uninfected cells before escaping from endosomes to reach the cytosol and bind PI(4,5)P2. It is not clear whether and how incoming Tat concentrates in uninfected cells. Here we show that, in uninfected cells, the S-acyl transferase DHHC-20 together with the prolylisomerases cyclophilin A (CypA) and FKBP12 palmitoylate Tat on Cys31 thereby increasing Tat affinity for PI(4,5)P2. In infected cells, CypA is bound by HIV-1 Gag, resulting in its encapsidation and CypA depletion from cells. Because of the lack of this essential cofactor, Tat is not palmitoylated in infected cells but strongly secreted. Hence, Tat palmitoylation specifically takes place in uninfected cells. Moreover, palmitoylation is required for Tat to accumulate at the plasma membrane and affect PI(4,5)P2-dependent membrane traffic such as phagocytosis and neurosecretion. |
| Publication | Nature Communications |
| Volume | 9 |
| Issue | 1 |
| Pages | 2251 |
| Date | 06 08, 2018 |
| Journal Abbr | Nat Commun |
| Language | eng |
| DOI | 10.1038/s41467-018-04674-y |
| ISSN | 2041-1723 |
| Library Catalog | PubMed |
| Extra | PMID: 29884859 PMCID: PMC5993824 |
| Tags | Acyltransferases, Animals, Animals, Newborn, author, Cell Membrane, Cyclophilin A, HEK293 Cells, HIV-1, Humans, Jurkat Cells, Lipoylation, Mice, Mice, Inbred C57BL, original, PC12 Cells, Phosphatidylinositol 4,5-Diphosphate, pp2i, Protein Binding, Rats, RAW 264.7 Cells, tat Gene Products, Human Immunodeficiency Virus |
| Date Added | 2019/06/04 - 17:21:49 |
| Date Modified | 2020/01/14 - 10:25:23 |
Institut de Recherche en Cancérologie de
