Hitchhiking on vesicles: a way to harness age‐related proteopathies?

Ahmadpour, Doryaneh; Babazadeh, Roja; Nyström, Thomas

doi:10.1111/febs.15345

Cited by 4 publications

(2 citation statements)

References 127 publications

(190 reference statements)

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“…In particular, STX5, GOSR1, YKT6 and BET1L make up the Cis-Golgi SNARE complex, and VAMP4 itself along with STX16, STX6 and VT1A make up the Trans-Golgi SNARE complex ( Climer et al , 2015 ). There is increasing evidence that these SNARE complexes, that regulate ER-Golgi transport, become disregulated in PD ( Ahmadpour et al , 2020 ; Martínez-Menárguez et al , 2019 ; Rendón et al , 2013 ).…”

Section: Resultsmentioning

confidence: 99%

GLIDER: function prediction from GLIDE-based neighborhoods

et al. 2022

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Motivation Protein function prediction, based on the patterns of connection in a Protein-Protein Interaction (or Association) network, is perhaps the most studied of the classical, fundamental inference problems for biological networks. A highly successful set of recent approaches use random walk-based low dimensional embeddings, that tend to place functionally similar proteins into coherent spatial regions. However, these approaches lose valuable local graph structure from the network when considering only the embedding. We introduce GLIDER, a method that replaces a protein-protein interaction or association network with a new graph-based similarity network. GLIDER is based on a variant of our previous GLIDE method, which was designed to predict missing links in Protein-Protein Association networks, capturing implicit local and global (i.e. embedding-based) graph properties. Results GLIDER outperforms competing methods on the task of predicting GO functional labels in cross-validation on a heterogeneous collection of four Human Protein-Protein Association networks derived from the 2016 DREAM Disease Module Identification Challenge, and also on three different protein-protein association networks built from the STRING database. We show that this is due to the strong functional enrichment that is present in the local GLIDER neighborhood in multiple different types of protein-protein association networks. Furthermore, we introduce the GLIDER graph neighborhood as a way for biologists to visualize the local neighborhood of a disease gene. As an application, we look at the local GLIDER neighborhoods of a set of known Parkinson’s Disease GWAS genes, rediscover many genes which have known involvement in Parkinson’s disease pathways, plus suggest some new genes to study. Availability All code is publicly available and can be accessed here: https://github.com/kap-devkota/GLIDER Supplementary information is available at Bioinformatics online.

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Section: Resultsmentioning

confidence: 99%

GLIDER: function prediction from GLIDE-based neighborhoods

et al. 2022

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“…Cells are constantly exposed to different kinds of stresses, such as exposure to sudden changes in temperature that can cause perturbations in protein homeostasis (proteostasis). The primary response of all cells to such a perturbation is elevating the levels of proteins, including molecular chaperones, involved in the refolding of misfolded proteins and proteins engaged in degrading the proteins that cannot be refolded [1–3]. The amplitude of the protein quality control (PQC) response is normally adapted to the severity of protein damage through an appropriate induction and feedback control of stress response genes [4].…”

Section: Introductionmentioning

confidence: 99%

Syntaxin 5‐dependent phosphorylation of the small heat shock protein Hsp42 and its role in protein quality control

et al. 2023

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The small heat shock protein Hsp42 and the t‐SNARE protein Sed5 have central roles in the sequestration of misfolded proteins into insoluble protein deposits in the yeast Saccharomyces cerevisiae. However, whether these proteins/processes interact in protein quality control (PQC) is not known. Here, we show that Sed5 and anterograde trafficking modulate phosphorylation of Hsp42 partially via the MAPK kinase Hog1. Such phosphorylation, specifically at residue S215, abrogated the co‐localization of Hsp42 with the Hsp104 disaggregase, aggregate clearance, chaperone activity, and sequestration of aggregates to IPOD and mitochondria. Furthermore, we found that Hsp42 is hyperphosphorylated in old cells leading to a drastic failure in disaggregation. Old cells also displayed a retarded anterograde trafficking, which, together with slow aggregate clearance and hyperphosphorylation of Hsp42, could be counteracted by Sed5 overproduction. We hypothesize that the breakdown of proper PQC during yeast aging may, in part, be due to a retarded anterograde trafficking leading to hyperphosphorylation of Hsp42.

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The yeast guanine nucleotide exchange factor Sec7 is a bottleneck in spatial protein quality control and detoxifies neurological disease proteins

Babazadeh,

Schneider,

Fischbach

et al. 2023

Sci Rep

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ER-to-Golgi trafficking partakes in the sorting of misfolded cytoplasmic proteins to reduce their cytological toxicity. We show here that yeast Sec7, a protein involved in proliferation of the Golgi, is part of this pathway and participates in an Hsp70-dependent formation of insoluble protein deposits (IPOD). Sec7 associates with the disaggregase Hsp104 during a mild heat shock and increases the rate of Hsp104 diffusion in an Hsp70-dependent manner when overproduced. Sec7 overproduction increased formation of IPODs from smaller aggregates and mitigated the toxicity of Huntingtin exon-1 upon heat stress while Sec7 depletion increased sensitivity to aẞ42 of the Alzheimer’s disease and α-synuclein of the Parkinson’s disease, suggesting a role of Sec7 in mitigating proteotoxicity.

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Hitchhiking on vesicles: a way to harness age‐related proteopathies?

Cited by 4 publications

References 127 publications

GLIDER: function prediction from GLIDE-based neighborhoods

GLIDER: function prediction from GLIDE-based neighborhoods

Syntaxin 5‐dependent phosphorylation of the small heat shock protein Hsp42 and its role in protein quality control

The yeast guanine nucleotide exchange factor Sec7 is a bottleneck in spatial protein quality control and detoxifies neurological disease proteins

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