P5B-ATPases in the mammalian polyamine transport system and their role in disease

Azfar, Mujahid; Veen, Sarah van; Houdou, Marine; Hamouda, Norin Nabil; Eggermont, Jan; Vangheluwe, Peter

doi:10.1016/j.bbamcr.2022.119354

Cited by 16 publications

(45 citation statements)

References 178 publications

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“…At 5 µM, the uptake of the BODIPY probes is lower compared with 14 Clabeled polyamines, especially for BODIPY-SPD. Our results therefore suggest that ATP13A3 presents a higher apparent affinity and/or reduced maximal uptake activity towards BODIPY-as compared to 14 C-labeled probes, similar to what we have observed for ATP13A2.…”

Section: Bodipy-conjugated Spm Is a Genuine Transport Substrate Of At...supporting

confidence: 88%

“…Finally, we compared BODIPY-SPM with radiolabeled spermine ( 14 C-SPM) uptake in A2 WT-OE cells to assess the impact of the fluorescent tag on cellular uptake capacities (Figure 2D). After incubating A2 WT-OE and D508N-OE cells for 30 min with either 5 µM of BODIPY-SPM or 14 C-SPM, we observed a significant 1.33-fold higher uptake for 14 C-SPM (Figure 2D). The effect of the fluorescent tag on SPM uptake reflects the higher apparent affinity, but lower Vmax of ATP13A2 for BODIPY-labeled versus native spermine (Figure 1C).…”

Section: Bodipy-conjugated Spm Is a Genuine Transport Substrate Of At...mentioning

confidence: 92%

“…CC-BY-ND 4.0 International license perpetuity. It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted December 15, 2022. ; https://doi.org/10.1101/2022.12.15.520427 doi: bioRxiv preprint (9.4-fold) versus 14 C-PUT (11-fold), whereas the uptake of BODIPY-SPD is significantly higher (21fold) than 14 C-SPD (11.6-fold). At 5 µM, the uptake of the BODIPY probes is lower compared with 14 Clabeled polyamines, especially for BODIPY-SPD.…”

Section: Bodipy-conjugated Spm Is a Genuine Transport Substrate Of At...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…In humans, ATP13A2 and ATP13A3 are ubiquitously expressed with highest expression in the brain and the liver, respectively ([14] and https://www.proteinatlas.org). At the subcellular level, both proteins are localized in the endosomal pathway with a preferred late endo-/lysosomal distribution for ATP13A2 [12–14] and early/recycling endosomes for ATP13A3 [12,13,15]. We provided biochemical evidence that human ATP13A2 (hATP13A2) transports polyamines from late endo/lysosomes to the cytosol with a high affinity for SPM and SPD [13], which was confirmed at the structural level [16–20].…”

Section: Introductionmentioning

confidence: 99%

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Novel green fluorescent polyamines to analyze ATP13A2 and ATP13A3 activity in the mammalian polyamine transport system

Houdou

Jacobs

Coene

et al. 2022

Preprint

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Cells acquire the polyamines putrescine (PUT), spermidine (SPD) and spermine (SPM) via the complementary action of polyamine uptake and synthesis pathways. The endosomal P5B-type ATPases ATP13A2 and ATP13A3 emerge as major determinants of mammalian polyamine uptake. Our biochemical evidence shows that fluorescently labeled polyamines are genuine substrates of ATP13A2. They can be used to measure polyamine uptake in ATP13A2 and ATP13A3-dependent cell models resembling radiolabeled polyamine uptake. We further report that ATP13A3 enables faster and stronger cellular polyamine uptake than ATP13A2. We also compared the uptake of new green-fluorescent PUT, SPD and SPM analogs using different coupling strategies (amide, triazole or isothiocyanate) and fluorophores (symmetrical BODIPY, BODIPY-FL and FITC). ATP13A2 promotes the uptake of various SPD and SPM analogs, whereas ATP13A3 mainly stimulates the uptake of PUT and SPD conjugates. However, the polyamine linker and coupling position on the fluorophore impacts the transport capacity, whereas replacing the fluorophore affects polyamine selectivity. The highest uptake in ATP13A2 or ATP13A3 cells is observed with BODIPY-FL-amide conjugated to SPD, whereas BODIPY-PUT analogs are specifically taken up via ATP13A3. We found that P5B-type ATPase isoforms transport fluorescently labeled polyamine analogs with a distinct structure-activity relationship (SAR) suggesting that isoform-specific polyamine probes can be designed.

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Section: Bodipy-conjugated Spm Is a Genuine Transport Substrate Of At...supporting

confidence: 88%

Section: Bodipy-conjugated Spm Is a Genuine Transport Substrate Of At...mentioning

confidence: 92%

Section: Bodipy-conjugated Spm Is a Genuine Transport Substrate Of At...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel green fluorescent polyamines to analyze ATP13A2 and ATP13A3 activity in the mammalian polyamine transport system

Houdou

Jacobs

Coene

et al. 2022

Preprint

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Kufor-Rakeb syndrome-associated psychosis: a novel loss-of-function ATP13A2 variant and response to antipsychotic therapy

Colijn,

Vrijsen,

et al. 2024

Neurogenetics

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Biallelic (autosomal recessive) pathogenic variants in ATP13A2 cause a form of juvenile-onset parkinsonism, termed Kufor-Rakeb syndrome. In addition to motor symptoms, a variety of other neurological and psychiatric symptoms may occur in affected individuals, including supranuclear gaze palsy and cognitive decline. Although psychotic symptoms are often reported, response to antipsychotic therapy is not well described in previous case reports/series. As such, we describe treatment response in an individual with Kufor-Rakeb syndrome-associated psychosis. His disease was caused by a homozygous novel loss-of-function ATP13A2 variant (NM_022089.4, c.1970_1975del) that was characterized in this study. Our patient exhibited a good response to quetiapine monotherapy, which he has so far tolerated well. We also reviewed the literature and summarized all previous descriptions of antipsychotic treatment response. Although its use has infrequently been described in Kufor-Rakeb syndrome, quetiapine is commonly used in other degenerative parkinsonian disorders, given its lower propensity to cause extrapyramidal symptoms. As such, quetiapine should be considered in the treatment of Kufor-Rakeb syndrome-associated psychosis when antipsychotic therapy is deemed necessary.

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Introducing the Special Issue on “Emerging Concepts & Non-Canonical Pathways in Cellular Signaling”

Bultynck

Khan

Schmitz

2023

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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P5B-ATPases in the mammalian polyamine transport system and their role in disease

Cited by 16 publications

References 178 publications

Novel green fluorescent polyamines to analyze ATP13A2 and ATP13A3 activity in the mammalian polyamine transport system

Novel green fluorescent polyamines to analyze ATP13A2 and ATP13A3 activity in the mammalian polyamine transport system

Kufor-Rakeb syndrome-associated psychosis: a novel loss-of-function ATP13A2 variant and response to antipsychotic therapy

Introducing the Special Issue on “Emerging Concepts & Non-Canonical Pathways in Cellular Signaling”

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