Heteromultimeric TRPML channel assemblies play a crucial role in the regulation of cell viability models and starvation-induced autophagy

Zeevi, David A.; Lev, Shaya; Frumkin, Ayala; Minke, Baruch; Bach, Gideon

doi:10.1242/jcs.067330

Cited by 57 publications

(51 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TRPML channels are able to heteromultimerize with each other. This has been shown by different groups (Venkatachalam et al, 2006;Zeevi et al, 2009Zeevi et al, , 2010Curcio-Morelli et al, 2010;Grimm et al, 2010). In addition, in vitro TRPML1/TRPML3 coexpression experiments indicated that TRPML1 is able to suppress TRPML3 activation by small-molecule agonists .…”

Section: Trpml Channels and Tpcs In Endolysosomal Cation Homeostasis 239mentioning

confidence: 61%

Role of TRPML and Two-Pore Channels in Endolysosomal Cation Homeostasis

Grimm¹,

Hassan²,

Wahl‐Schott³

et al. 2012

J Pharmacol Exp Ther

View full text Add to dashboard Cite

The transient receptor potential (TRP) channels TRPML1, TRPML2, and TRPML3 (also called mucolipins 1-3 or MCOLN1-3) are nonselective cation channels. Mutations in the Trpml1 gene cause mucolipidosis type IV in humans with clinical features including psychomotor retardation, corneal clouding, and retinal degeneration, whereas mutations in the Trpml3 gene cause deafness, circling behavior, and coat color dilution in mice. No disease-causing mutations are reported for the Trpml2 gene. Like TRPML channels, which are expressed in the endolysosomal pathway, two-pore channels (TPCs), namely TPC1, TPC2, and TPC3, are found in intracellular organelles, in particular in endosomes and lysosomes. Both TRPML channels and TPCs may function as calcium/cation release channels in endosomes, lysosomes, and lysosome-related organelles with TRPMLs being activated by phosphatidylinositol 3,5-bisphosphate and regulated by pH and TPCs being activated by nicotinic acid adenine dinucleotide phosphate in a calcium-and pH-dependent manner. They may also be involved in endolysosomal transport and fusion processes, e.g., as intracellular calcium sources. Currently, however, the exact physiological roles of TRPML channels and TPCs remain quite elusive, and whether TRPML channels are purely endolysosomal ion channels or whether they may also be functionally active at the plasma membrane in vivo remains to be determined.

show abstract

Section: Trpml Channels and Tpcs In Endolysosomal Cation Homeostasis 239mentioning

confidence: 61%

Role of TRPML and Two-Pore Channels in Endolysosomal Cation Homeostasis

Grimm¹,

Hassan²,

Wahl‐Schott³

et al. 2012

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…In recent years, TRPML1 has been characterized using electrophysiological tools and its basic cation channel properties have been investigated [9][10][11][12][13][14][15][16][17][18][19] , its protein-protein interaction network has been explored [20][21][22][23][24] , and knockout mouse models have been generated and investigated [25][26][27][28] . However, effective treatment options for MLIV patients are still missing.…”

mentioning

confidence: 99%

A small molecule restores function to TRPML1 mutant isoforms responsible for mucolipidosis type IV

et al. 2014

View full text Add to dashboard Cite

“…NAADP as a potent Ca 2+ mobilizing messenger, which targets the TRPMLs or TPCs and triggers Ca 2+ release from the endolysosomal stores [19]. As we known, the members of the TRPML constitute a family of evolutionarily conserved cation channels that play crucial roles in endolysosomal vesicles [20] [49]. TRPMLs localize to endolysosomes and facilitate Ca 2+ -dependent fusion between autophagosomes and lysosomes resulting in lysosomal degradation of autophagic material [20].…”

Section: The Negative Regulation Of Cd38 In Autophagymentioning

confidence: 99%

Dual Roles of CD38 in Autophagy

Wang¹,

Song²,

Wu³

et al. 2017

View full text Add to dashboard Cite

CD38 is a versatile, ubiquitously expressed protein that was identified as a multifunctional enzyme. Recently, cumulating evidence has suggested that CD38 is involved in autophagy, which is an evolutionarily conserved lysosomal degradation and recycling system. Acting as a enzyme, CD38 utilizes nicotinamide adenine dinucleotide phosphate (NADP) to synthesize nicotinic acid adenine dinucleotide phosphate (NAADP), which acts as a key messenger for Ca 2+ -mobilizing in lysosome by targeting two-pore channels (TPCs) or transient receptor potential mucolipins (TRPMLs). Multiple studies have indicated that CD38 is involved in autophagy by modulating intracellular Ca 2+ signaling. However, the control of autophagy by CD38 signaling is the subject of two contrary views. The autophagosomes trafficking and fusion with lysosomes to form autolysosomes are crucial steps in autophagy. On the one hand, the available evidence indicates that lysosome trafficking and fusion to autophagosomes is positively modulated by CD38. On the other hand, overexpression of TPC2, which is positively modulated by CD38, was shown to promote the accumulation of autophagosomes, thus suppress autophagy. This review will reveal the interesting contrary dual roles of CD38 in autophagy, and critical insight into the molecular mechanisms of CD38 in autophagy regulation.

show abstract

Heteromultimeric TRPML channel assemblies play a crucial role in the regulation of cell viability models and starvation-induced autophagy

Cited by 57 publications

References 49 publications

Role of TRPML and Two-Pore Channels in Endolysosomal Cation Homeostasis

Role of TRPML and Two-Pore Channels in Endolysosomal Cation Homeostasis

A small molecule restores function to TRPML1 mutant isoforms responsible for mucolipidosis type IV

Dual Roles of CD38 in Autophagy

Contact Info

Product

Resources

About