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