Polyamine-transporting ATPase 13A2

Definition:

ATPase which acts as a lysosomal polyamine exporter with high affinity for spermine. Also stimulates cellular uptake of polyamines and protects against polyamine toxicity. Plays a role in intracellular cation homeostasis and the maintenance of neuronal integrity. Contributes to cellular zinc homeostasis. Confers cellular protection against Mn(2+) and Zn(2+) toxicity and mitochondrial stress. Required for proper lysosomal and mitochondrial maintenance. Regulates the autophagy-lysosome pathway through the control of SYT11 expression at both transcriptional and post-translational levels. Facilitates recruitment of deacetylase HDAC6 to lysosomes to deacetylate CTTN, leading to actin polymerization, promotion of autophagosome-lysosome fusion and completion of autophagy. Promotes secretion of exosomes as well as secretion of SCNA via exosomes. Plays a role in lipid homeostasis.

References:

[1]. Sarah van Veen, et al. ATP13A2 deficiency disrupts lysosomal polyamine export. Nature. 2020 Feb;578(7795):419-424. [Content Brief]

[2]. Taiji Tsunemi, et al. ATP13A2/PARK9 regulates secretion of exosomes and α-synuclein. J Neurosci. 2014 Nov 12;34(46):15281-7. [Content Brief]

[3]. Tine Holemans, et al. A lipid switch unlocks Parkinson's disease-associated ATP13A2. Proc Natl Acad Sci U S A. 2015 Jul 21;112(29):9040-5. [Content Brief]

[4]. Ruoxi Wang, et al. ATP13A2 facilitates HDAC6 recruitment to lysosome to promote autophagosome-lysosome fusion. J Cell Biol. 2019 Jan 7;218(1):267-284. [Content Brief]

[5]. Carla F Bento, et al. The Parkinson's disease-associated genes ATP13A2 and SYT11 regulate autophagy via a common pathway. Nat Commun. 2016 Jun 9;7:11803. [Content Brief]

[6]. Alejandra Lucía Marcos, et al. The Parkinson-associated human P5B-ATPase ATP13A2 modifies lipid homeostasis. Biochim Biophys Acta Biomembr. 2019 Oct 1;1861(10):182993. [Content Brief]

[7]. Anne Grünewald, et al. ATP13A2 mutations impair mitochondrial function in fibroblasts from patients with Kufor-Rakeb syndrome. Neurobiol Aging. 2012 Aug;33(8):1843.e1-7. [Content Brief]

[8]. Alejandro Estrada-Cuzcano, et al. Loss-of-function mutations in the ATP13A2/PARK9 gene cause complicated hereditary spastic paraplegia (SPG78). Brain. 2017 Feb;140(2):287-305. [Content Brief]

[9]. David Ramonet, et al. PARK9-associated ATP13A2 localizes to intracellular acidic vesicles and regulates cation homeostasis and neuronal integrity. Hum Mol Genet. 2012 Apr 15;21(8):1725-43. [Content Brief]

[10]. Stephanie M Y Kong, et al. Parkinson's disease-linked human PARK9/ATP13A2 maintains zinc homeostasis and promotes α-Synuclein externalization via exosomes. Hum Mol Genet. 2014 Jun 1;23(11):2816-33. [Content Brief]

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