TRP Channels as Interior Designers: Remodeling the Endolysosomal Compartment in Natural Killer Cells
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...
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| Format: | Article |
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Frontiers Media S.A.
2020-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00753/full |
| _version_ | 1819207465434087424 |
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| author | Dennis Clement Dennis Clement Jodie P. Goodridge Christian Grimm Sandip Patel Karl-Johan Malmberg Karl-Johan Malmberg Karl-Johan Malmberg |
| author_facet | Dennis Clement Dennis Clement Jodie P. Goodridge Christian Grimm Sandip Patel Karl-Johan Malmberg Karl-Johan Malmberg Karl-Johan Malmberg |
| author_sort | Dennis Clement |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T05:23:55Z |
| format | Article |
| id | doaj.art-9dd96ce0e4144afea1abe4990f87a06e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T05:23:55Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9dd96ce0e4144afea1abe4990f87a06e2022-12-21T17:58:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-04-011110.3389/fimmu.2020.00753531406TRP Channels as Interior Designers: Remodeling the Endolysosomal Compartment in Natural Killer CellsDennis Clement0Dennis Clement1Jodie P. Goodridge2Christian Grimm3Sandip Patel4Karl-Johan Malmberg5Karl-Johan Malmberg6Karl-Johan Malmberg7The KG Jebsen Center for Cancer Immunotherapy, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Cancer Immunology, Oslo University Hospital, Institute for Cancer Research, Oslo, NorwayFate Therapeutics Inc., San Diego, CA, United StatesFaculty of Medicine, Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität, Munich, GermanyDepartment of Cell and Developmental Biology, University College London, London, United KingdomThe KG Jebsen Center for Cancer Immunotherapy, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Cancer Immunology, Oslo University Hospital, Institute for Cancer Research, Oslo, NorwayDepartment of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, SwedenCytotoxic 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.https://www.frontiersin.org/article/10.3389/fimmu.2020.00753/fullNK cellTRP cation channelsecretory lysosomescytotoxic lymphocytesmucolipincalcium signaling |
| spellingShingle | Dennis Clement Dennis Clement Jodie P. Goodridge Christian Grimm Sandip Patel Karl-Johan Malmberg Karl-Johan Malmberg Karl-Johan Malmberg TRP Channels as Interior Designers: Remodeling the Endolysosomal Compartment in Natural Killer Cells Frontiers in Immunology NK cell TRP cation channel secretory lysosomes cytotoxic lymphocytes mucolipin calcium signaling |
| title | TRP Channels as Interior Designers: Remodeling the Endolysosomal Compartment in Natural Killer Cells |
| title_full | TRP Channels as Interior Designers: Remodeling the Endolysosomal Compartment in Natural Killer Cells |
| title_fullStr | TRP Channels as Interior Designers: Remodeling the Endolysosomal Compartment in Natural Killer Cells |
| title_full_unstemmed | TRP Channels as Interior Designers: Remodeling the Endolysosomal Compartment in Natural Killer Cells |
| title_short | TRP Channels as Interior Designers: Remodeling the Endolysosomal Compartment in Natural Killer Cells |
| title_sort | trp channels as interior designers remodeling the endolysosomal compartment in natural killer cells |
| topic | NK cell TRP cation channel secretory lysosomes cytotoxic lymphocytes mucolipin calcium signaling |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00753/full |
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