PMID- 29079589 OWN - NLM STAT- MEDLINE DCOM- 20180614 LR - 20180718 IS - 2470-9468 (Electronic) IS - 2470-9468 (Linking) VI - 2 IP - 16 DP - 2017 Oct 27 TI - Lysosome signaling controls the migration of dendritic cells. LID - eaak9573 [pii] LID - 10.1126/sciimmunol.aak9573 [doi] AB - Dendritic cells (DCs) patrol their environment by linking antigen acquisition by macropinocytosis to cell locomotion. DC activation upon bacterial sensing inhibits macropinocytosis and increases DC migration, thus promoting the arrival of DCs to lymph nodes for antigen presentation to T cells. The signaling events that trigger such changes are not fully understood. We show that lysosome signaling plays a critical role in this process. Upon bacterial sensing, lysosomal calcium is released by the ionic channel TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1), which activates the actin-based motor protein myosin II at the cell rear, promoting fast and directional migration. Lysosomal calcium further induces the activation of the transcription factor EB (TFEB), which translocates to the nucleus to maintain TRPML1 expression. We found that the TRPML1-TFEB axis results from the down-regulation of macropinocytosis after bacterial sensing by DCs. Lysosomal signaling therefore emerges as a hitherto unexpected link between macropinocytosis, actomyosin cytoskeleton organization, and DC migration. CI - Copyright (c) 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. FAU - Bretou, Marine AU - Bretou M AUID- ORCID: 0000-0002-7841-3775 AD - INSERM U932 Immunite et Cancer, Institut Curie, Paris Sciences & Lettres Research University, F-75248 Paris, Cedex 05, France. marine.bretou@curie.fr pablo.vargas@curie.fr amlennon@curie.fr. FAU - Saez, Pablo J AU - Saez PJ AUID- ORCID: 0000-0003-0521-9426 AD - INSERM U932 Immunite et Cancer, Institut Curie, Paris Sciences & Lettres Research University, F-75248 Paris, Cedex 05, France. AD - Institut Curie, Paris Sciences & Lettres Research University, CNRS, UMR 144, F-75005 Paris, France. AD - Institut Pierre-Gilles de Gennes, Paris Sciences & Lettres Research University, F-75005 Paris, France. FAU - Sanseau, Doriane AU - Sanseau D AUID- ORCID: 0000-0002-9427-2458 AD - INSERM U932 Immunite et Cancer, Institut Curie, Paris Sciences & Lettres Research University, F-75248 Paris, Cedex 05, France. FAU - Maurin, Mathieu AU - Maurin M AUID- ORCID: 0000-0003-3555-6247 AD - INSERM U932 Immunite et Cancer, Institut Curie, Paris Sciences & Lettres Research University, F-75248 Paris, Cedex 05, France. FAU - Lankar, Danielle AU - Lankar D AD - INSERM U932 Immunite et Cancer, Institut Curie, Paris Sciences & Lettres Research University, F-75248 Paris, Cedex 05, France. FAU - Chabaud, Melanie AU - Chabaud M AD - INSERM U932 Immunite et Cancer, Institut Curie, Paris Sciences & Lettres Research University, F-75248 Paris, Cedex 05, France. FAU - Spampanato, Carmine AU - Spampanato C AD - Telethon Institute of Genetics and Medicine (TIGEM), I-80078 Pozzuoli, Naples, Italy. FAU - Malbec, Odile AU - Malbec O AUID- ORCID: 0000-0002-3159-1558 AD - INSERM U932 Immunite et Cancer, Institut Curie, Paris Sciences & Lettres Research University, F-75248 Paris, Cedex 05, France. FAU - Barbier, Lucie AU - Barbier L AUID- ORCID: 0000-0001-7102-3566 AD - Institut Curie, Paris Sciences & Lettres Research University, CNRS, UMR 144, F-75005 Paris, France. AD - Institut Pierre-Gilles de Gennes, Paris Sciences & Lettres Research University, F-75005 Paris, France. AD - Universite Paris-Sud, Universite Paris-Saclay, F-91405 Orsay, France. FAU - Muallem, Shmuel AU - Muallem S AD - Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Maiuri, Paolo AU - Maiuri P AUID- ORCID: 0000-0001-5079-445X AD - Institut Curie, Paris Sciences & Lettres Research University, CNRS, UMR 144, F-75005 Paris, France. AD - Institut Pierre-Gilles de Gennes, Paris Sciences & Lettres Research University, F-75005 Paris, France. AD - Institute FIRC (Italian Foundation for Cancer Research) of Molecular Oncology (IFOM-FIRC), I-20139 Milano, Italy. AD - Istituto di Genetica Molecolare-Consiglio Nazionale delle Ricerche (IGM-CNR), Via Abbiategrasso 207, I-27100 Pavia, Italy. FAU - Ballabio, Andrea AU - Ballabio A AUID- ORCID: 0000-0003-1381-4604 AD - Telethon Institute of Genetics and Medicine (TIGEM), I-80078 Pozzuoli, Naples, Italy. AD - Medical Genetics, Department of Translational Medicine, Federico II University, I-80131 Naples, Italy. AD - Department of Molecular and Human Genetics, Baylor College of Medicine and Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA. FAU - Helft, Julie AU - Helft J AUID- ORCID: 0000-0002-2733-1972 AD - INSERM U932 Immunite et Cancer, Institut Curie, Paris Sciences & Lettres Research University, F-75248 Paris, Cedex 05, France. FAU - Piel, Matthieu AU - Piel M AUID- ORCID: 0000-0002-2848-177X AD - Institut Curie, Paris Sciences & Lettres Research University, CNRS, UMR 144, F-75005 Paris, France. AD - Institut Pierre-Gilles de Gennes, Paris Sciences & Lettres Research University, F-75005 Paris, France. FAU - Vargas, Pablo AU - Vargas P AUID- ORCID: 0000-0002-6475-494X AD - INSERM U932 Immunite et Cancer, Institut Curie, Paris Sciences & Lettres Research University, F-75248 Paris, Cedex 05, France. marine.bretou@curie.fr pablo.vargas@curie.fr amlennon@curie.fr. AD - Institut Curie, Paris Sciences & Lettres Research University, CNRS, UMR 144, F-75005 Paris, France. AD - Institut Pierre-Gilles de Gennes, Paris Sciences & Lettres Research University, F-75005 Paris, France. FAU - Lennon-Dumenil, Ana-Maria AU - Lennon-Dumenil AM AUID- ORCID: 0000-0002-8220-4482 AD - INSERM U932 Immunite et Cancer, Institut Curie, Paris Sciences & Lettres Research University, F-75248 Paris, Cedex 05, France. marine.bretou@curie.fr pablo.vargas@curie.fr amlennon@curie.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Sci Immunol JT - Science immunology JID - 101688624 RN - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors) RN - 0 (Mcoln1 protein, mouse) RN - 0 (Tcfeb protein, mouse) RN - 0 (Transient Receptor Potential Channels) RN - EC 3.6.1.- (Myosin Type II) RN - SY7Q814VUP (Calcium) SB - IM CIN - Nat Rev Immunol. 2017 Dec;17(12):730-731. PMID: 29129914 MH - Animals MH - Antigen Presentation MH - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics/metabolism MH - Calcium/metabolism MH - Cell Differentiation MH - *Cell Movement MH - Cell Nucleus/metabolism MH - Cytoskeleton/metabolism MH - Dendritic Cells/*immunology/physiology MH - Down-Regulation MH - Lysosomes/immunology/*metabolism MH - Mice MH - Myosin Type II/genetics/metabolism MH - Pinocytosis MH - *Signal Transduction MH - Transient Receptor Potential Channels/deficiency/genetics/metabolism EDAT- 2017/10/29 06:00 MHDA- 2018/06/15 06:00 CRDT- 2017/10/29 06:00 PHST- 2016/09/20 00:00 [received] PHST- 2017/05/26 00:00 [revised] PHST- 2017/09/20 00:00 [accepted] PHST- 2017/10/29 06:00 [entrez] PHST- 2017/10/29 06:00 [pubmed] PHST- 2018/06/15 06:00 [medline] AID - 2/16/eaak9573 [pii] AID - 10.1126/sciimmunol.aak9573 [doi] PST - ppublish SO - Sci Immunol. 2017 Oct 27;2(16):eaak9573. doi: 10.1126/sciimmunol.aak9573.