Dataset Information

BUB-1 targets PP2A:B56 to regulates chromosome congression during meiosis I in C. elegans oocytes

ABSTRACT: This project consisted in identifying phosphorylated residues in BUB-1 in C. elegans embryo extract. This is part of our general interest in identifying PTMs playing a role during meiosis.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Caenorhabditis Elegans

TISSUE(S): Embryo

SUBMITTER: Douglas Lamont

LAB HEAD: Dr Federico Pelisch

PROVIDER: PXD023258 | Pride | 2021-08-23

REPOSITORIES: Pride

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BUB-1 targets PP2A:B56 to regulate chromosome congression during meiosis I in C. elegans oocytes.

Bel Borja Laura L Soubigou Flavie F Taylor Samuel J P SJP Fraguas Bringas Conchita C Budrewicz Jacqueline J Lara-Gonzalez Pablo P Sorensen Turpin Christopher G CG Bembenek Joshua N JN Cheerambathur Dhanya K DK Pelisch Federico F

eLife 20201223

Protein Phosphatase 2A (PP2A) is a heterotrimer composed of scaffolding (A), catalytic (C), and regulatory (B) subunits. PP2A complexes with B56 subunits are targeted by Shugoshin and BUBR1 to protect centromeric cohesion and stabilise kinetochore-microtubule attachments in yeast and mouse meiosis. In Caenorhabditis elegans, the closest BUBR1 orthologue lacks the B56-interaction domain and Shugoshin is not required for meiotic segregation. Therefore, the role of PP2A in C. elegans ...[more]

PMID: 33355089

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Project description:Equine grass sickness (EGS) is an acute, predominantly fatal, multiple system neuropathy of grazing horses with reported incidence rates of approximately 2%. An apparently identical disease occurs in multiple species including but not limited to cats, dogs, and rabbits. Although the precise aetiology remains unclear, ultrastructural findings have suggested that the primary lesion lies in the glycoprotein biosynthetic pathway of specific neuronal populations. The goal of this study was therefore to identify the molecular processes underpinning neurodegeneration in EGS. Here we use a bottom up approach beginning with the application of modern proteomic tools to the analysis of cranial (superior) cervical ganglion (CCG – a consistently affected tissue) from EGS affected patients and appropriate control cases postmortem. In what appears to be the first proteomic application of modern proteomic tools to equine neuronal tissues and/or to an inherent neurodegenerative disease of large animals (not a model of human disease), we identified 2311 proteins in CCG extracts, with 320 proteins increased and 186 decreased by greater than 20% relative to controls. Further examination of selected proteomic candidates by quantitative fluorescent western blotting (QFWB) and sub-cellular expression profiling by immunohistochemistry, highlighted a previously unreported dysregulation in proteins commonly associated with protein misfolding/aggregation responses seen in a myriad of human neurodegenerative conditions, including but not limited to amyloid precursor protein (APP), microtubule associated protein (Tau) and multiple components of the ubiquitin proteasome system (UPS). Differentially expressed proteins eligible for in silico pathway analysis clustered predominantly into the following biofunctions: 1. Diseases & disorders including; neurological disease, skeletal & muscular disorders; 2. Molecular and cellular functions: including cellular assembly & organisation, cell-to-cell signalling and interaction (including epinephrine, dopamine & adrenergic signalling and receptor function) and small molecule biochemistry. Interestingly, whilst the biofunctions identified in this study may represent pathways underpinning EGS induced neurodegeneration, this is also the first demonstration of potential molecular conservation (including previously unreported dysregulation of the UPS and APP) spanning the degenerative cascades from an apparently unrelated condition of large animals, to small animal models with altered neuronal vulnerability, and human neurological conditions. Importantly, this study highlights the feasibility and benefits of applying modern proteomic techniques to veterinary investigations of neurodegenerative processes in diseases of large animals.

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	F264980.dat	Other
	F264999.dat	Other
	F265978.dat	Other
	F265979.dat	Other
	FP_GFP_TOP.raw	Raw

Dataset Information

BUB-1 targets PP2A:B56 to regulates chromosome congression during meiosis I in C. elegans oocytes

Dataset's files

Publications

BUB-1 targets PP2A:B56 to regulate chromosome congression during meiosis I in <i>C. elegans</i> oocytes.

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