An Ancestral Deuterostome Family of Two-pore Channels Mediates Nicotinic Acid Adenine Dinucleotide Phosphate-dependent Calcium Release from Acidic Organelles

Brǎiloiu, Eugen; Hooper, Robert; Cai, Xinjiang; Brailoiu, G. Cristina; Keebler, Michael V.; Dun, Nae J.; Marchant, Jonathan S.; Patel, Sandip

doi:10.1074/jbc.c109.081943

Cited by 113 publications

(143 citation statements)

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“…However, co-expression of TPC2delN with TRPML1delNC did not affect Ca 2ϩ influx induced by TRPML1delNC (Fig. 3C) (16,40). Fig.…”

Section: Resultsmentioning

confidence: 99%

“…TPC1 is expressed in endosomes, lysosomes (14,16), and other yet undefined organelles, whereas TPC2 is expressed in late endosomes and lysosomes (14,16). Importantly, overexpression of human TPC1 (16) or human/mouse TPC2 (13,14,40) potentiates NAADP-mediated Ca 2ϩ increase. Similar results were obtained with sea urchin TPCs (40,41).…”

Section: Camentioning

confidence: 99%

“…Importantly, overexpression of human TPC1 (16) or human/mouse TPC2 (13,14,40) potentiates NAADP-mediated Ca 2ϩ increase. Similar results were obtained with sea urchin TPCs (40,41). Knockdown of human TPC1 and overexpression of TPC1 mutated in a predicted pore region (L273P) inhibits endogenous NAADP response in SKBR3 cells (16).…”

Section: Camentioning

confidence: 99%

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Transient Receptor Potential Mucolipin 1 (TRPML1) and Two-pore Channels Are Functionally Independent Organellar Ion Channels

Yamaguchi

Jha

et al. 2011

Journal of Biological Chemistry

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104

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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 ( ؊/؊ 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. Ca2ϩ plays a major role in the function of intracellular organelles including biosynthesis and membrane trafficking (1, 2). Although the mechanism controlling Ca 2ϩ in the endoplasmic reticulum has been studied extensively, very little is known about Ca 2ϩ homeostasis by other organelles. Furthermore, although accumulating evidence indicates that acidic organelles such as endosomes and lysosomes are dynamic Ca 2ϩ stores, the molecular basis for Ca 2ϩ release from these so-called "acidic Ca 2ϩ stores" (3) is at present defined poorly. By far, the best characterized route for mobilization of acidic Ca 2ϩ stores is through the production of the potent Ca 2ϩ -releasing second messenger, nicotinic acid adenine dinucleotide phosphate (NAADP) 5 (4). The Ca 2ϩ -mobilizing properties of NAADP were discovered in sea urchin eggs (5), in which NAADP was shown to mobilize Ca 2ϩ not from the endoplasmic reticulum but instead from lysosome-related organelles (6). Its effects have subsequently been extended to a variety of cell types, including pancreatic acinar and ␤ cells, smooth muscle cells, neurons, and breast cancer cells (4). NAADP is produced by several extracellular stimuli in an agonist-specific manner and implicated in a number of physiological responses, including fertilization, glucose sensing, exocytosis, and neuronal growth (4). Deregulated lysosomal Ca 2ϩ signaling may also result in disease (2,7,8). Despite the physiological and potential pathophysiological importance of NAADP signaling, the molecular identity of the NAADP receptor is not entirely clear (9). Recently, members of the transient receptor potential mucolipin (TRPML) (10, 11) and two-pore channel (TPC) (12-16) families, which are all present in the endo/lysosomal system, have been proposed as candidates.TRPMLs form a subfamily of the superfamily of the TRP channels. The founding member is TRPML1, which was ide...

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“…However, co-expression of TPC2delN with TRPML1delNC did not affect Ca 2ϩ influx induced by TRPML1delNC (Fig. 3C) (16,40). Fig.…”

Section: Resultsmentioning

confidence: 99%

Section: Camentioning

confidence: 99%

See 1 more Smart Citation

Transient Receptor Potential Mucolipin 1 (TRPML1) and Two-pore Channels Are Functionally Independent Organellar Ion Channels

Yamaguchi

Jha

et al. 2011

Journal of Biological Chemistry

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104

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“…Measurements of intracellular Ca 2ϩ concentrations were performed as previously described (8). Briefly, cells were incubated with 5 M fura-2 AM (Invitrogen, Carlsbad, CA) in HBSS at room temperature for 45 min, in the dark, washed three times with dye-free HBSS, and then incubated for another 45 min to allow for complete deesterification of the dye.…”

Section: Methodsmentioning

confidence: 99%

“…Injections were performed using Femtotips II, InjectMan NI2, and FemtoJet systems (Eppendorf) as previously reported (8). Pipettes were back filled with an intracellular solution composed of 110 mM KCl, 10 mM NaCl, and 20 mM HEPES (pH 7.2) (14) or angiotensin II.…”

Section: Methodsmentioning

confidence: 99%

Intracellular angiotensin II activates rat myometrium

Deliu

Tica

Motoc

et al. 2011

American Journal of Physiology-Cell Physiology

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Deliu E, Tica AA, Motoc D, Brailoiu GC, Brailoiu E. Intracellular angiotensin II activates rat myometrium. Am J Physiol Cell Physiol 301: C559 -C565, 2011. First published May 22, 2011; doi:10.1152/ajpcell.00123.2011.-Angiotensin II is a modulator of myometrial activity; both AT1 and AT2 receptors are expressed in myometrium. Since in other tissues angiotensin II has been reported to activate intracellular receptors, we assessed the effects of intracellular administration of angiotensin II via microinjection on myometrium, using calcium imaging. Intracellular injection of angiotensin II increased cytosolic Ca 2ϩ concentration ([Ca 2ϩ ]i) in myometrial cells in a dose-dependent manner. The effect was abolished by the AT 1 receptor antagonist losartan but not by the AT2 receptor antagonist PD-123319. Disruption of the endo-lysosomal system, but not that of Golgi apparatus, prevented the angiotensin II-induced increase in [Ca 2ϩ ]i. Blockade of AT1 receptor internalization had no effect, whereas blockade of microautophagy abolished the increase in [Ca 2ϩ ]i produced by intracellular injection of angiotensin II; this indicates that microautophagy is a critical step in transporting the peptide into the endo-lysosomes lumenum. The response to angiotensin II was slightly reduced in Ca 2ϩ -free saline, indicating a major involvement of Ca 2ϩ release from internal stores. Blockade of inositol 1,4,5-trisphosphate (IP 3) receptors with heparin and xestospongin C or inhibition of phospholipase C (PLC) with U-73122 abolished the response to angiotensin II, supporting the involvement of PLC-IP 3 pathway. Angiotensin II-induced increase in [Ca 2ϩ ]i was slightly reduced by antagonism of ryanodine receptors. Taken together, our results indicate for the first time that in myometrial cells, intracellular angiotensin II activates AT 1-like receptors on lysosomes and activates PLC-IP 3-dependent Ca 2ϩ release from endoplasmic reticulum; the response is further augmented by a Ca 2ϩ -induced Ca 2ϩ release mechanism via ryanodine receptors activation. calcium imaging; cytosolic calcium concentration; endoplasmic reticulum; microinjection ANGIOTENSIN II is an eight amino acid peptide that exerts its actions by activation of G protein-coupled receptors, namely AT 1 and AT 2 receptors. Increasing evidence suggests that angiotensin II acts not only as an endocrine/paracrine factor, but also as an autacoid or intracrine peptide, with the ability to signal from within the cell, without stimulating plasma membrane receptors (21, 38). We previously reported that intracellular administration of angiotensin II via liposomes increases contractility of rat aorta via activation of intracellular receptors (7). Similarly, microinjection of angiotensin II increases cytosolic Ca 2ϩ concentration ([Ca 2ϩ ] i ) in vascular smooth muscle cells (13, 16) or kidney proximal tubule cells (49). The intracellular angiotensin II can result either via uptake from the interstitium or by intracellular synthesis. In the latter case, intracellular renin conver...

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Two‐pore channels (TPCs): Current controversies

2013

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Much excitement surrounded the proposal that a family of endo-lysosomal channels, the two-pore channels (TPCs) were the long sought after targets of the Ca(2+) -mobilising messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). However, the role of TPCs in NAADP signalling may be more complex than originally envisaged. First, NAADP may not bind directly to TPCs but via an accessory protein. Second, two papers recently challenged the notion that TPCs are NAADP-regulated Ca(2+) channels by suggesting that they are highly selective Na(+) channels regulated by the lipid phosphatidylinositol 3,5-bisphosphate and by ATP. This paper aims critically to evaluate the evidence for TPCs as NAADP targets and to discuss how the new findings fit in with what we know about endo-lysosomal Ca(2+) stores.

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An Ancestral Deuterostome Family of Two-pore Channels Mediates Nicotinic Acid Adenine Dinucleotide Phosphate-dependent Calcium Release from Acidic Organelles

Cited by 113 publications

References 21 publications

Transient Receptor Potential Mucolipin 1 (TRPML1) and Two-pore Channels Are Functionally Independent Organellar Ion Channels

Transient Receptor Potential Mucolipin 1 (TRPML1) and Two-pore Channels Are Functionally Independent Organellar Ion Channels

Intracellular angiotensin II activates rat myometrium

Two‐pore channels (TPCs): Current controversies

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