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.
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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.
| Type: | Article |
|---|---|
| Title: | TRP Channels as Interior Designers: Remodeling the Endolysosomal Compartment in Natural Killer Cells |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2020.00753 |
| Publisher version: | http://doi.org/10.3389/fimmu.2020.00753 |
| Language: | English |
| Additional information: | © 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/). |
| Keywords: | NK cell, TRP cation channel, secretory lysosomes, cytotoxic lymphocytes, mucolipin, calcium signaling |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10099233 |
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