Ca2+/H+ exchange by acidic organelles regulates cell migration in vivo

Melchionda, Manuela; Pittman, Jon K.; Mayor, Roberto; Patel, Sandip

doi:10.1083/jcb.201510019

Cited by 94 publications

(80 citation statements)

References 49 publications

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“…The advantage of many of these non‐plant CAX models, such as Xenopus CAX (Melchionda et al . 2016) or Plasmodium CAX (Guttery et al . 2013), is that the CAXs are encoded by single genes in these species and therefore genetic dissection of CAX Ca 2+ signalling is not hampered by genetic compensation and redundancy challenges.…”

Section: Discussionmentioning

confidence: 99%

“…2016). The first animal CAX to be functionally examined was a zebrafish ( Danio rerio ) CAX, shown to be required for neural crest development, potentially through modulation of pH and Ca 2+ homeostasis (Manohar et al .…”

Section: Non‐plant Caxs – Lessons To Be Learned?mentioning

confidence: 99%

“…Subsequently, a frog ( Xenopus laevis ) CAX has also been found expressed in neural crest cells and required for cell migration, by controlling the formation of stable focal adhesions during cell spreading (Melchionda et al . 2016). Moreover, this study demonstrated that the animal CAX, localised at acidic lysosomes, regulates cytosolic Ca 2+ signals.…”

Section: Non‐plant Caxs – Lessons To Be Learned?mentioning

confidence: 99%

“…2012; Melchionda et al . 2016). For plant CAXs, direct observation and confirmation of CAX‐dependent Ca 2+ signal modulation has so far been challenging.…”

Section: Non‐plant Caxs – Lessons To Be Learned?mentioning

confidence: 99%

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CAX‐ing a wide net: Cation/H⁺ transporters in metal remediation and abiotic stress signalling

2016

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Cation/proton exchangers (CAXs) are a class of secondary energised ion transporter that are being implicated in an increasing range of cellular and physiological functions. CAXs are primarily Ca2+ efflux transporters that mediate the sequestration of Ca2+ from the cytosol, usually into the vacuole. Some CAX isoforms have broad substrate specificity, providing the ability to transport trace metal ions such as Mn2+ and Cd2+, as well as Ca2+. In recent years, genomic analyses have begun to uncover the expansion of CAXs within the green lineage and their presence within non‐plant species. Although there appears to be significant conservation in tertiary structure of CAX proteins, there is diversity in function of CAXs between species and individual isoforms. For example, in halophytic plants, CAXs have been recruited to play a role in salt tolerance, while in metal hyperaccumulator plants CAXs are implicated in cadmium transport and tolerance. CAX proteins are involved in various abiotic stress response pathways, in some cases as a modulator of cytosolic Ca2+ signalling, but in some situations there is evidence of CAXs acting as a pH regulator. The metal transport and abiotic stress tolerance functions of CAXs make them attractive targets for biotechnology, whether to provide mineral nutrient biofortification or toxic metal bioremediation. The study of non‐plant CAXs may also provide insight into both conserved and novel transport mechanisms and functions.

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Section: Discussionmentioning

confidence: 99%

Section: Non‐plant Caxs – Lessons To Be Learned?mentioning

confidence: 99%

Section: Non‐plant Caxs – Lessons To Be Learned?mentioning

confidence: 99%

“…2012; Melchionda et al . 2016). For plant CAXs, direct observation and confirmation of CAX‐dependent Ca 2+ signal modulation has so far been challenging.…”

Section: Non‐plant Caxs – Lessons To Be Learned?mentioning

confidence: 99%

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CAX‐ing a wide net: Cation/H⁺ transporters in metal remediation and abiotic stress signalling

2016

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“…They are likely filled by Ca 2+ -H + exchange (Melchionda et al, 2016) and express members of the transient receptor potential mucolipin (TRPML) and two-pore channel (TPC) families to effect Ca 2+ release (Grimm et al, 2012; Kiselyov et al, 2012; Patel, 2015; Waller-Evans and Lloyd-Evans, 2015). Three TRPML isoforms are present in humans (García-Añoveros and Wiwatpanit, 2014).…”

Section: Introductionmentioning

confidence: 99%

Endo-lysosomal TRP mucolipin-1 channels trigger global ER Ca2+ release and Ca2+ influx

Kilpatrick

Yates

Grimm

et al. 2016

Journal of Cell Science

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Transient receptor potential (TRP) mucolipins (TRPMLs), encoded by the MCOLN genes, are patho-physiologically relevant endo-lysosomal ion channels crucial for membrane trafficking. Several lines of evidence suggest that TRPMLs mediate localised Ca2+ release but their role in Ca2+ signalling is not clear. Here, we show that activation of endogenous and recombinant TRPMLs with synthetic agonists evoked global Ca2+ signals in human cells. These signals were blocked by a dominant-negative TRPML1 construct and a TRPML antagonist. We further show that, despite a predominant lysosomal localisation, TRPML1 supports both Ca2+ release and Ca2+ entry. Ca2+ release required lysosomal and ER Ca2+ stores suggesting that TRPMLs, like other endo-lysosomal Ca2+ channels, are capable of ‘chatter’ with ER Ca2+ channels. Our data identify new modalities for TRPML1 action.

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Laponite Lights Calcium Flickers by Reprogramming Lysosomes to Steer DC Migration for An Effective Antiviral CD8⁺ T‐Cell Response

Li,

Hou,

et al. 2023

Advanced Science

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Immunotherapy using dendritic cell (DC)‐based vaccination is an established approach for treating cancer and infectious diseases; however, its efficacy is limited. Therefore, targeting the restricted migratory capacity of the DCs may enhance their therapeutic efficacy. In this study, the effect of laponite (Lap) on DCs, which can be internalized into lysosomes and induce cytoskeletal reorganization via the lysosomal reprogramming–calcium flicker axis, is evaluated, and it is found that Lap dramatically improves the in vivo homing ability of these DCs to lymphoid tissues. In addition, Lap improves antigen cross‐presentation by DCs and increases DC‐T‐cell synapse formation, resulting in enhanced antigen‐specific CD8+ T‐cell activation. Furthermore, a Lap‐modified cocktail (Lap@cytokine cocktail [C‐C]) is constructed based on the gold standard, C‐C, as an adjuvant for DC vaccines. Lap@C‐C‐adjuvanted DCs initiated a robust cytotoxic T‐cell immune response against hepatitis B infection, resulting in > 99.6% clearance of viral DNA and successful hepatitis B surface antigen seroconversion. These findings highlight the potential value of Lap as a DC vaccine adjuvant that can regulate DC homing, and provide a basis for the development of effective DC vaccines.

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Ca2+/H+ exchange by acidic organelles regulates cell migration in vivo

Abstract: A vertebrate Ca2+/H+ exchanger (CAX), which is part of a widespread conserved family in animals, localizes to acidic organelles, tempers evoked Ca2+ signals, and regulates cell-matrix adhesion during neural crest cell migration.

Cited by 94 publications

References 49 publications

CAX‐ing a wide net: Cation/H⁺ transporters in metal remediation and abiotic stress signalling

CAX‐ing a wide net: Cation/H⁺ transporters in metal remediation and abiotic stress signalling

Endo-lysosomal TRP mucolipin-1 channels trigger global ER Ca2+ release and Ca2+ influx

Laponite Lights Calcium Flickers by Reprogramming Lysosomes to Steer DC Migration for An Effective Antiviral CD8⁺ T‐Cell Response

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Ca2+/H+ exchange by acidic organelles regulates cell migration in vivo

Abstract: A vertebrate Ca2+/H+ exchanger (CAX), which is part of a widespread conserved family in animals, localizes to acidic organelles, tempers evoked Ca2+ signals, and regulates cell-matrix adhesion during neural crest cell migration.

Cited by 94 publications

References 49 publications

CAX‐ing a wide net: Cation/H+ transporters in metal remediation and abiotic stress signalling

CAX‐ing a wide net: Cation/H+ transporters in metal remediation and abiotic stress signalling

Endo-lysosomal TRP mucolipin-1 channels trigger global ER Ca2+ release and Ca2+ influx

Laponite Lights Calcium Flickers by Reprogramming Lysosomes to Steer DC Migration for An Effective Antiviral CD8+ T‐Cell Response

Contact Info

Product

Resources

About

CAX‐ing a wide net: Cation/H⁺ transporters in metal remediation and abiotic stress signalling

CAX‐ing a wide net: Cation/H⁺ transporters in metal remediation and abiotic stress signalling

Laponite Lights Calcium Flickers by Reprogramming Lysosomes to Steer DC Migration for An Effective Antiviral CD8⁺ T‐Cell Response