eprintid: 10099233 rev_number: 17 eprint_status: archive userid: 608 dir: disk0/10/09/92/33 datestamp: 2020-06-02 10:39:09 lastmod: 2021-10-04 01:28:35 status_changed: 2020-06-02 10:39:09 type: article metadata_visibility: show creators_name: Clement, D creators_name: Goodridge, JP creators_name: Grimm, C creators_name: Patel, S creators_name: Malmberg, K-J title: TRP Channels as Interior Designers: Remodeling the Endolysosomal Compartment in Natural Killer Cells ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: F96 keywords: NK cell, TRP cation channel, secretory lysosomes, cytotoxic lymphocytes, mucolipin, calcium signaling note: © 2020 Clement, Goodridge, Grimm, Patel and Malmberg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). abstract: Cytotoxic lymphocytes, including natural killer (NK) cells and T cells are distinguished by their ability to eliminate target cells through release of secretory lysosomes. Conventional lysosomes and secretory lysosomes are part of the pleomorphic endolysosomal system and characterized by its highly dynamic nature. Several calcium-permeable TRP calcium channels play an essential role in endolysosomal calcium signaling to ensure proper function of these organelles. In NK cells, the expression of self MHC-specific inhibitory receptors dynamically tunes their secretory potential in a non-transcriptional, calcium-dependent manner. New insights suggest that TRPML1-mediated lysosomal calcium fluxes are tightly interconnected to NK cell functionality through modulation of granzyme B and perforin content of the secretory lysosome. Lysosomal TRP channels show a subset-specific expression pattern during NK differentiation, which is paralleled with gradually increased loading of effector molecules in secretory lysosomes. Methodological advances, including organellar patch-clamping, specific pharmacological modulators, and genetically-encoded calcium indicators open up new possibilities to investigate how TRP channels influence communication between intracellular organelles in immune cells. This review discusses our current understanding of lysosome biogenesis in NK cells with an emphasis on the TRP mucolipin family and the implications for NK cell functionality and cancer immunotherapy. date: 2020-04 date_type: published publisher: FRONTIERS MEDIA SA official_url: http://doi.org/10.3389/fimmu.2020.00753 oa_status: green full_text_type: pub pmcid: PMC7198808 language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1782119 doi: 10.3389/fimmu.2020.00753 lyricists_name: Patel, Sandip lyricists_id: SKPAT56 actors_name: Patel, Sandip actors_id: SKPAT56 actors_role: owner full_text_status: public publication: Frontiers in Immunology volume: 11 article_number: 753 pages: 15 issn: 1664-3224 citation: Clement, D; Goodridge, JP; Grimm, C; Patel, S; Malmberg, K-J; (2020) TRP Channels as Interior Designers: Remodeling the Endolysosomal Compartment in Natural Killer Cells. Frontiers in Immunology , 11 , Article 753. 10.3389/fimmu.2020.00753 <https://doi.org/10.3389/fimmu.2020.00753>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10099233/1/TRP%20Channels%20as%20Interior%20Designers%20Remodeling%20the%20Endolysosomal%20Compartment%20in%20Natural%20Killer%20Cells.pdf