TRPML and lysosomal function

Zeevi, David A.; Frumkin, Ayala; Bach, Gideon

doi:10.1016/j.bbadis.2007.01.004

Cited by 80 publications

(99 citation statements)

References 62 publications

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“…To test this possibility, we used a TRP-ML1 specific polyclonal antibody to examine if the channel activity could be blocked. It has been reported that TRP-ML1 wide-type is a 580-amino acid protein with six transmembrane domain and the C terminus of this channel protein is the feature functional domain of the transient receptor potential cation channel family (19,51). The anti-TRP-ML1 antibody used in the current experiments was raised against a peptide mapping at the C terminus of TRP-PL1 of mouse origin.…”

Section: Discussionmentioning

confidence: 99%

Reconstitution and Characterization of a Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP)-sensitive Ca2+ Release Channel from Liver Lysosomes of Rats

Zhang

2007

Journal of Biological Chemistry

121

108

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Nicotinic acid adenine dinucleotide phosphate (NAADP) is capable of inducing global Ca2؉ increases via a lysosome-associated mechanism, but the mechanism mediating NAADP-induced intracellular Ca 2؉ release remains unclear. The present study reconstituted and characterized a lysosomal NAADP-sensitive Ca 2؉ release channel using purified lysosomes from rat liver. Furthermore, the identity of lysosomal NAADP-sensitive Ca 2؉ release channels was also investigated. It was found that NAADP activates lysosomal Ca 2؉ release channels at concentrations of 1 nM to 1 M, but this activating effect of NAADP was significantly reduced when the concentrations used increased to 10 or 100 M. Either activators or blockers of Ca 2؉ release channels on the sarcoplasmic reticulum (SR) had no effect on the activity of these NAADP-activated Ca 2؉ release channels. Interestingly, the activity of this lysosomal NAADP-sensitive Ca 2؉ release channel increased when the pH in cis solution decreased, but it could not be inhibited by a lysosomal H ؉ -ATPase antagonist, bafilomycin A1. However, the activity of this channel was significantly inhibited by plasma membrane L-type Ca 2؉ channel blockers such as verapamil, diltiazem, and nifedipine, or the nonselective Ca 2؉ , Na ؉ channel blocker, amiloride. In addition, blockade of TRP-ML1 (transient receptor potential-mucolipin 1) protein by anti-TRP-ML1 antibody markedly attenuated NAADP-induced activation of these lysosomal Ca 2؉ channels. These results for the first time provide direct evidence that a NAADP-sensitive Ca 2؉ release channel is present in the lysosome of native liver cells and that this channel is associated with TRP-ML1, which is different from ER/SR Ca 2؉ release channels.

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Section: Discussionmentioning

confidence: 99%

Reconstitution and Characterization of a Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP)-sensitive Ca2+ Release Channel from Liver Lysosomes of Rats

Zhang

2007

Journal of Biological Chemistry

121

108

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“…The TRPML family was established with the identification of TRPML1. 47,48 TRPML1, the first member of the mucolipins, was cloned in 1999, as a result of genetic analyses of patient tissues with a genetic disease called Mucolipidosis type IV (MLIV). 49,50 MLIV is a lysosomal storage disease linked to buildup of poorly characterized material throughout the patient's tissue in the form of storage bodies.…”

Section: Intracellular Membrane Fusionmentioning

confidence: 99%

“…A number of excellent review articles on TRPML channels published recently provide comprehensive analysis of TRPML localization, traffic and possible function. 47,48,[53][54][55] In the present review, we will focus on their Ca 2+ transport function and the evidence for its role in membrane fusion.…”

Section: Intracellular Membrane Fusionmentioning

confidence: 99%

The intracellular Ca²⁺channels of membrane traffic

et al. 2012

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The exquisite timing of neurotransmitter release is a key determinant of neuronal function. It is an excellent example of a signal-centric paradigm involving interpretation and amplification of an incoming signal. As in all signaling systems, amplification in this model improves fidelity and timing of signaling. The Ca 2+ -dependence of synaptic vesicle release is a necessary requirement for translating action potentials into a release of neuromediators. The flooding of SNARE docking complexes by Ca 2+ entering the cell through voltage-gated Ca 2+ channels, followed by conformational changes that ultimately drive membrane fusion, is responsible for the incredibly robust and rapid neurotransmitter release in response to electrical stimulation.1 This signal-interpretation-response paradigm however remains largely unresolved in critical cellular processes involving other intracellular membrane organelles such as endosomes and lysosomes. However, several recent developments, primarily stemming from identification and characterization of new Regulation of organellar fusion and fission by Ca 2+ has emerged as a central paradigm in intracellular membrane traffic. Originally formulated for Ca 2+ -driven SNARE-mediated exocytosis in the presynaptic terminals, it was later expanded to explain membrane traffic in other exocytic events within the endo-lysosomal system. The list of processes and conditions that depend on the intracellular membrane traffic includes aging, antigen and lipid processing, growth factor signaling and enzyme secretion. Characterization of the ion channels that regulate intracellular membrane fusion and fission promises novel pharmacological approaches in these processes when their function becomes aberrant. The recent identification of Ca 2+ permeability through the intracellular ion channels comprising the mucolipin (TRPMLs) and the twopore channels (TPCs) families pinpoints the candidates for the Ca 2+ channel that drive intracellular membrane traffic. The present review summarizes the recent developments and the current questions relevant to this topic.

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“…TRPML family: The TRPML family (see Qian and Noben-Trauth, 2005;Cantiello et al, 2005;Zeevi et al, 2007) consists of three mammalian members (TRPML1-3). TRPML channels are probably restricted to intracellular vesicles and mutations in the gene (MCOLN1) encoding TRPML1 (mucolipin-1) are the cause of the neurodegenerative disorder mucolipidosis type IV (MLIV) in man.…”

Section: Transient Receptor Potential (Trp) Cationmentioning

confidence: 99%