VPS35 haploinsufficiency increases Alzheimer's disease neuropathology

Li, Wen; Tang, Fulei; Hong, Yan; Luo, Shuhong; Wang, Chunlei; He, Wanxia; Shen, Chengyong; Jung, Ji-Ung; Xiong, Fei; Lee, Daehoon; Zhang, Quanguang; Brann, Darrell W.; Kim, Tae‐Wan; Yan, Riqiang; Ma, Lin; Xiong, Wen-Cheng

doi:10.1084/jem20813oia35

Cited by 59 publications

(96 citation statements)

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“…Moreover, there is increasing realization that perturbed CSC function is linked to a number of human diseases. CSC deficiency plays a role in nonamyloidogenic versus amyloidogenic processing of amyloid precursor protein (APP) (He et al 2005;Small et al 2005;Muhammad et al 2008;Wen et al 2011;Choy et al 2012) and the pathogenesis of Alzheimer's disease (Siegenthaler and Rajendran 2012). In addition, a specific VPS35 mutation, Asp620Asn, has been linked to late-onset autosomal-dominant familial Parkinson's disease (Vilariño-Güell et al 2011;Zimprich et al 2011), the loci for human VPS26A has been genetically associated with type 2 diabetes in South Asians (Kooner et al 2011), and the endosomal transport of various pathogens (Salmonella, Herpesvirus saimiri, Coxiella burnetii, human papillomavirus, Legionella pneumophila) and toxins (Shiga toxin) is also mediated in part by the CSC Popoff et al 2007;Kingston et al 2011;Finsel et al 2013;Lipovsky et al 2013;McDonough et al 2013).…”

Section: The Diversity Of Retromer Function In Cell Function and Orgamentioning

confidence: 99%

Retromer: A Master Conductor of Endosome Sorting

Burd

Cullen

2014

Cold Spring Harbor Perspectives in Biology

395

440

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The endosomal network comprises an interconnected network of membranous compartments whose primary function is to receive, dissociate, and sort cargo that originates from the plasma membrane and the biosynthetic pathway. A major challenge in cell biology is to achieve a thorough molecular description of how this network operates, and in so doing, how defects contribute to the etiology and pathology of human disease. We discuss the increasing body of evidence that implicates an ancient evolutionary conserved complex, termed "retromer," as a master conductor in the complex orchestration of multiple cargo-sorting events within the endosomal network.

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Section: The Diversity Of Retromer Function In Cell Function and Orgamentioning

confidence: 99%

Retromer: A Master Conductor of Endosome Sorting

Burd

Cullen

2014

Cold Spring Harbor Perspectives in Biology

395

440

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“…Loss of retromer function increases amyloidogenic processing of APP, and studies of tissue from AD patients indicates that retromer expression could be downregulated in neuronal tissue, although the underlying cause is presently unknown (Small et al, 2005;Muhammad et al, 2008;Lane et al, 2010;Wen et al, 2011). It has also been shown recently that specific variants of the Snx3 and Rab7a genes are genetically linked to late-onset AD (Vardarajan et al, 2012).…”

Section: Retromer and Diseasementioning

confidence: 99%

The retromer complex – endosomal protein recycling and beyond

Seaman

2012

Journal of Cell Science

414

434

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SummaryThe retromer complex is a vital element of the endosomal protein sorting machinery that is conserved across all eukaryotes. Retromer is most closely associated with the endosome-to-Golgi retrieval pathway and is necessary to maintain an active pool of hydrolase receptors in the trans-Golgi network. Recent progress in studies of retromer have identified new retromer-interacting proteins, including the WASH complex and cargo such as the Wntless/MIG-14 protein, which now extends the role of retromer beyond the endosome-to-Golgi pathway and has revealed that retromer is required for aspects of endosome-to-plasma membrane sorting and regulation of signalling events. The interactions between the retromer complex and other macromolecular protein complexes now show how endosomal protein sorting is coordinated with actin assembly and movement along microtubules, and place retromer squarely at the centre of a complex set of protein machinery that governs endosomal protein sorting. Dysregulation of retromer-mediated endosomal protein sorting leads to various pathologies, including neurodegenerative diseases such as Alzheimer disease and spastic paraplegia and the mechanisms underlying these pathologies are starting to be understood. In this Commentary, I will highlight recent advances in the understanding of retromer-mediated endosomal protein sorting and discuss how retromer contributes to a diverse set of physiological processes.

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“…Retromer and SNX27 have been shown to recycle a wide range of surface molecules, ranging from signalling receptors like the β2-adrenergic receptor (Lauffer et al, 2010) or the parathyroid hormone receptor (PTHR) (Chan et al, 2016;McGarvey et al, 2016), and nutrient transporters (Steinberg et al, 2013) to neuronal glutamate receptors (Wang et al, 2013;Loo et al, 2014;Hussain et al, 2014). Although loss of retromer as well as of the WASH complex is lethal early in embryogenesis (Wen et al, 2011;Gomez et al, 2012), loss of SNX27 is lethal shortly upon birth of genetically modified mice (Cai et al, 2011), highlighting the physiological relevance of SNX27-, retromer-and/or WASH-driven recycling processes. In this context, recent genome-wide association studies have identified mutations in the retromer subunit VPS35 as the underlying cause for late-onset hereditary Parkinsonism, with the point mutation of aspartate 620 to asparagine (D620N) being the most significant one (VilarinoGuell et al, 2011;Zimprich et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Retromer- and WASH-dependent sorting of nutrient transporters requires a multivalent interaction network with ANKRD50

Kvainickas

Orgaz

Nägele

et al. 2017

Journal of Cell Science

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Retromer and the associated actin-polymerizing WASH complex are essential for the endocytic recycling of a wide range of integral membrane proteins. A hereditary Parkinson's-disease-causing point mutation (D620N) in the retromer subunit VPS35 perturbs retromer's association with the WASH complex and also with the uncharacterized protein ankyrin-repeat-domain-containing protein 50 (ANKRD50). Here, we firmly establish ANKRD50 as a new and essential component of the SNX27-retromer-WASH super complex. Depletion of ANKRD50 in HeLa or U2OS cells phenocopied the loss of endosome-to-cell-surface recycling of multiple transmembrane proteins seen upon suppression of SNX27, retromer or WASHcomplex components. Mass-spectrometry-based quantification of the cell surface proteome of ANKRD50-depleted cells identified amino acid transporters of the SLC1A family, among them SLC1A4, as additional cargo molecules that depend on ANKRD50 and retromer for their endocytic recycling. Mechanistically, we show that ANKRD50 simultaneously engages multiple parts of the SNX27-retromer-WASH complex machinery in a direct and co-operative interaction network that is needed to efficiently recycle the nutrient transporters GLUT1 (also known as SLC2A1) and SLC1A4, and potentially many other surface proteins.

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VPS35 haploinsufficiency increases Alzheimer's disease neuropathology

Cited by 59 publications

References 1 publication

Retromer: A Master Conductor of Endosome Sorting

Retromer: A Master Conductor of Endosome Sorting

The retromer complex – endosomal protein recycling and beyond

Retromer- and WASH-dependent sorting of nutrient transporters requires a multivalent interaction network with ANKRD50

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