ArticleThe Journal of biological chemistry2011
Transient receptor potential mucolipin 1 (TRPML1) and two-pore channels are functionally independent organellar ion channels.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 101 citations in OpenAlex.
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- Transcriptional Dysregulation of Autophagy in Aging and Potential Interventions: Insights Into TFEB and FOXOs.Frontiers in bioscience (Landmark edition) · 2025Review
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- OCaR1 endows exocytic vesicles with autoregulatory competence by preventing uncontrolled Ca2+ release, exocytosis, and pancreatic tissue damage.The Journal of clinical investigation · 2024Article
- Two-pore channel-2 and inositol trisphosphate receptors coordinate CaCell reports · 2024Article
- Pseudorabies virus inhibits progesterone-induced inactivation of TRPML1 to facilitate viral entry.PLoS pathogens · 2024Article
- Endolysosomal transient receptor potential mucolipins and two-pore channels: implications for cancer immunity.Frontiers in immunology · 2024Review
- Modulation of Lysosomal ClCells · 2023Article
- NAADP-Dependent TPC Current.Handbook of experimental pharmacology · 2023Article
- Review
- Two-pore channel blockade by phosphoinositide kinase inhibitors YM201636 and PI-103 determined by a histidine residue near pore-entrance.Communications biology · 2022Article
- Diversity of two-pore channels and the accessory NAADP receptors in intracellular CaCell calcium · 2022Review
- Targeting the two-pore channel 2 in cancer progression and metastasis.Exploration of targeted anti-tumor therapy · 2022Review
- Advances in Intracellular Calcium Signaling Reveal Untapped Targets for Cancer Therapy.Biomedicines · 2021Review
- Lsm12 is an NAADP receptor and a two-pore channel regulatory protein required for calcium mobilization from acidic organelles.Nature communications · 2021Article
- Lysosomal TRPML1 Channel: Implications in Cardiovascular and Kidney Diseases.Advances in experimental medicine and biology · 2021Article
- NAADP: From Discovery to Mechanism.Frontiers in immunology · 2021Review
- Roles of NADMolecules (Basel, Switzerland) · 2020Review
- Early evidence of delayed oligodendrocyte maturation in the mouse model of mucolipidosis type IV.Disease models & mechanisms · 2020Article
- Lysosomal CaCold Spring Harbor perspectives in biology · 2020Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
NAADP is a potent second messenger that mobilizes Ca(2+) from acidic organelles such as endosomes and lysosomes. The molecular basis for Ca(2+) release by NAADP, however, is uncertain. TRP mucolipins (TRPMLs) and two-pore channels (TPCs) are Ca(2+)-permeable ion channels present within the endolysosomal system. Both have been proposed as targets for NAADP. In the present study, we probed possible physical and functional association of these ion channels. Exogenously expressed TRPML1 showed near complete colocalization with TPC2 and partial colocalization with TPC1. TRPML3 overlap with TPC2 was more modest. TRPML1 and to some extent TRPML3 co-immunoprecipitated with TPC2 but less so with TPC1. Current recording, however, showed that TPC1 and TPC2 did not affect the activity of wild-type TRPML1 or constitutively active TRPML1(V432P). N-terminally truncated TPC2 (TPC2delN), which is targeted to the plasma membrane, also failed to affect TRPML1 and TRPML1(V432P) channel function or TRPML1(V432P)-mediated Ca(2+) influx. Whereas overexpression of TPCs enhanced NAADP-mediated Ca(2+) signals, overexpression of TRPML1 did not, and the dominant negative TRPML1(D471K) was without affect on endogenous NAADP-mediated Ca(2+) signals. Furthermore, the single channel properties of NAADP-activated TPC2delN were not affected by TRPML1. Finally, NAADP-evoked Ca(2+) oscillations in pancreatic acinar cells were identical in wild-type and TRPML1(-/-) cells. We conclude that although TRPML1 and TPCs are present in the same complex, they function as two independent organellar ion channels and that TPCs, not TRPMLs, are the targets for NAADP.
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