Essential and selective role of SNX12 in transport of endocytic and retrograde cargo

Priya, Amulya; Sugatha, Jini; Parveen, Sameena; Lacas‐Gervais, Sandra; Raj, Prateek; Gilleron, Jérôme; Datta, Soma

doi:10.1242/jcs.201905

Cited by 21 publications

(24 citation statements)

References 82 publications

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“…We also demonstrated that the retrograde transport of CI-M6PR through ETCs tethered by GCC88 was perturbed in the absence of SNX3. This observation is consistent with previous reports that RNAi knockdown of SNX3 alters CI-M6PR retrograde transport (Harbour et al, 2010; Priya et al, 2017). SNX3 interacts with the retromer subunits Vps35 and Vps26 via multiple interfaces through its N-terminal tail, and this molecular interaction enables the endosomal recruitment of retromer via the SNX3 PX domain (Harterink et al, 2011; Vardarajan et al, 2012; Harrison et al, 2014; Lucas et al, 2016; Lenoir et al, 2018).…”

Section: Discussionsupporting

confidence: 94%

Retromer has a selective function in cargo sorting via endosome transport carriers

Cui

Carosi

Yang

et al. 2018

Journal of Cell Biology

132

154

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Retromer is a peripheral membrane protein complex that coordinates multiple vesicular trafficking events within the endolysosomal system. Here, we demonstrate that retromer is required for the maintenance of normal lysosomal morphology and function. The knockout of retromer subunit Vps35 causes an ultrastructural alteration in lysosomal structure and aberrant lysosome function, leading to impaired autophagy. At the whole-cell level, knockout of retromer Vps35 subunit reduces lysosomal proteolytic capacity as a consequence of the improper processing of lysosomal hydrolases, which is dependent on the trafficking of the cation-independent mannose 6-phosphate receptor (CI-M6PR). Incorporation of CI-M6PR into endosome transport carriers via a retromer-dependent process is restricted to those tethered by GCC88 but not golgin-97 or golgin-245. Finally, we show that this retromer-dependent retrograde cargo trafficking pathway requires SNX3, but not other retromer-associated cargo binding proteins, such as SNX27 or SNX-BAR proteins. Therefore, retromer does contribute to the retrograde trafficking of CI-M6PR required for maturation of lysosomal hydrolases and lysosomal function.

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Section: Discussionsupporting

confidence: 94%

Retromer has a selective function in cargo sorting via endosome transport carriers

Cui

Carosi

Yang

et al. 2018

Journal of Cell Biology

132

154

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“…SNX3‐Retromer is involved in the retrograde transport of cargo receptors including the Wnt sorting receptor Wntless, transferrin receptor, the divalent metal ion transporter Dmt1‐II, and CI‐MPR, in carriers that are morphologically and functionally distinct from the SNX‐BAR proteins in higher eukaryotes . It has also been suggested that the SNX3 homologue SNX12 can perform a similar role . The crystal structure of a complex of SNX3, Vps26 and Vps35 bound to a short peptide motif from the Dmt1‐II protein reveals the mechanism for these cargo interactions (Figure A).…”

Section: Snx Proteins As Retromer Cargo Adaptorsmentioning

confidence: 99%

Towards a molecular understanding of endosomal trafficking by Retromer and Retriever

Chen

Healy

Collins

2019

Traffic

158

144

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www.traf c.dkCover legend: Retromer is essen al in all eukaryotes for the traffi cking of transmembrane proteins within membrane tubules. Cryoelectron microscopy was used to show how retromer assembles with membrane-bound sor ng nexin proteins to form these membrane tubules. The picture shows a modelled segment of the retromersor ng nexin coat. See Chen et al. (Traffi c 2019; 20(7):465-478). Read the full ar cle on Aim and ScopeTraffic encourages and facilitates the publication of papers covering the cell biology of intracellular transport in health and disease. Areas of interest include protein, nucleic acid and lipid traffic, molecular motors, intracellular pathogens, intracellular proteolysis, nuclear import and export, cytokinesis and the cell cycle, protein translocation, antigen processing and presentation, organelle biogenesis, metabolism, cell polarity and organization, and organelle movement.All aspects of the structural, molecular biology, biochemistry, genetics, morphology, intracellular signaling and relationship to hereditary or infectious diseases will be covered. Manuscripts must provide a clear conceptual or mechanistic advance. The editors will reject papers that require major changes, including addition of significant experimental data or other significant revision.

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“…SNX12 is predominantly expressed in brain tissues and SNX12 levels are significantly decreased in the human AD brains ( Zhao et al, 2012 ), indicating a possible link between SNX12 and AD. Further studies reveal that SNX12 resides in early endosomes ( Pons et al, 2012 ; Priya et al, 2017 ) and directly interacts with BACE1 ( Zhao et al, 2012 ) ( Figure 1 ) to modulate BACE1 endocytosis, thereby affecting APP β-cleavage and Aβ production ( Zhao et al, 2012 ).…”

Section: The Retromer Complex and Snxs In Neurodegenerative Diseasesmentioning

confidence: 99%

The Retromer Complex and Sorting Nexins in Neurodegenerative Diseases

Zhang

Huang

Hong

et al. 2018

Front. Aging Neurosci.

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The retromer complex and associated sorting nexins (SNXs) comprise a critical trafficking machinery which mediates endosomal protein sorting. Retromer and/or SNX dysfunction has been linked to several neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), and Down’s syndrome (DS). In AD, deficiency of the retromer complex or its cargo proteins impairs endosomal trafficking of amyloid precursor protein (APP), resulting in the overproduction of β-amyloid (Aβ). Several SNX components directly interact with APP or APP-cleaving enzymes (β- and γ-secretases) to regulate amyloidogenic APP processing and Aβ generation. In addition, PD-linked mutations in retromer components cause mistrafficking of retromer cargo proteins and mitochondrial dysfunction, and dysregulation retromer-mediated trafficking has been considered as an important cause of hereditary spastic paraplegia (HSP) and neuronal ceroid lipofuscinoses (NCLs). Moreover, SNX27 deficiency is an important contributor for synaptic and cognitive impairment in DS. Here we review recent findings describing the retromer complex and/or SNXs-mediated endosomal sorting in neurodegenerative disorders.

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Essential and selective role of SNX12 in transport of endocytic and retrograde cargo

Cited by 21 publications

References 82 publications

Retromer has a selective function in cargo sorting via endosome transport carriers

Retromer has a selective function in cargo sorting via endosome transport carriers

Towards a molecular understanding of endosomal trafficking by Retromer and Retriever

The Retromer Complex and Sorting Nexins in Neurodegenerative Diseases

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