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Adaptation to Stressors by Systemic Protein Amyloidogenesis.

ABSTRACT: The amyloid state of protein organization is typically associated with debilitating human neuropathies and is seldom observed in physiology. Here, we uncover a systemic program that leverages the amyloidogenic propensity of proteins to regulate cell adaptation to stressors. On stimulus, cells assemble the amyloid bodies (A-bodies), nuclear foci containing heterogeneous proteins with amyloid-like biophysical properties. A discrete peptidic sequence, termed the amyloid-converting motif (ACM), is capable of targeting proteins to the A-bodies by interacting with ribosomal intergenic noncoding RNA (rIGSRNA). The pathological ?-amyloid peptide, involved in Alzheimer's disease, displays ACM-like activity and undergoes stimuli-mediated amyloidogenesis in vivo. Upon signal termination, elements of the heat-shock chaperone pathway disaggregate the A-bodies. Physiological amyloidogenesis enables cells to store large quantities of proteins and enter a dormant state in response to stressors. We suggest that cells have evolved a post-translational pathway that rapidly and reversibly converts native-fold proteins to an amyloid-like solid phase.

SUBMITTER: Audas TE

PROVIDER: S-EPMC5098424 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Adaptation to Stressors by Systemic Protein Amyloidogenesis.

Audas Timothy E TE Audas Danielle E DE Jacob Mathieu D MD Ho J J David JJ Khacho Mireille M Wang Miling M Perera J Kishan JK Gardiner Caroline C Bennett Clay A CA Head Trajen T Kryvenko Oleksandr N ON Jorda Mercé M Daunert Sylvia S Malhotra Arun A Trinkle-Mulcahy Laura L Gonzalgo Mark L ML Lee Stephen S

Developmental cell 20161006 2

The amyloid state of protein organization is typically associated with debilitating human neuropathies and is seldom observed in physiology. Here, we uncover a systemic program that leverages the amyloidogenic propensity of proteins to regulate cell adaptation to stressors. On stimulus, cells assemble the amyloid bodies (A-bodies), nuclear foci containing heterogeneous proteins with amyloid-like biophysical properties. A discrete peptidic sequence, termed the amyloid-converting motif (ACM), is c ...[more]

PMID: 27720612

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Project description:BackgroundRheumatic and Musculoskeletal Diseases (RMDs) substantially impact the lives of patients, with complex associations between disease severity and self-perceived health status. In this regard, the Coping with Rheumatic Stressors (CORS) questionnaire was developed to measure how patients with RMDs cope with stressors such as pain, limitations or dependency. The CORS is not currently available in Spanish, and therefore the adaptation of this instrument is needed.ObjectiveFirst, to cross-culturally adapt the CORS into Spanish for Spain. Secondly, to test the conceptual equivalence of the translated version in patients with axial spondyloarthritis (axSpA).MethodsA translation of the CORS into Spanish was performed adhering to the forward-backward procedure described by Beaton. Two translators produced independent forward translations of the item content, response options, and instructions of the CORS into Spanish. Both versions were harmonized in a consensual version. Another translator back-translated the synthesized version into Dutch. A scientific committee including all the translators, one methodologist and a rheumatologist, held a meeting and reached consensus on discrepancies to develop a final draft version of the Spanish CORS. Then, a field test with cognitive debriefing was conducted, involving a sample of 10 patients with axSpA.ResultsThe translation process of the CORS was completed after the discussion of some discrepancies throughout the process. The first translation was done without major complications. Back-translation presented some discrepancies. These led to minor modifications in the wording in one response option and 15 questionnaire items. The scientific committee agreed upon a final version of the questionnaire. Cognitive debriefing, led to minor modifications; for example, three respondents indicated that one of the statements in the instructions was syntactically complex ("indique cuán a menudo usted ha llevado a cabo dicho comportamiento") which led to its adjustment. The process indicated that the final CORS Spanish questionnaire was clear and understandable to all patients.ConclusionsThe Spanish version of the CORS showed good cross-cultural validity and good face validity according to the field test. Before the Spanish CORS is implemented, further validation is in progress to test the psychometric properties of the instrument in patients with axSpA.

Project description:Chlamydomonas reinhardtii is one of the most important model organisms nowadays phylogenetically situated between higher plants and animals (Merchant et al. 2007). Stress adaptation of this unicellular model algae is in the focus because of its relevance to biomass and biofuel production. Here, we have studied cold stress adaptation of C. reinhardtii hitherto not described for this algae whereas intensively studied in higher plants. Toward this goal, high throughput mass spectrometry was employed to integrate proteome, metabolome, physiological and cell-morphological changes during a time-course from 0 to 120 h. These data were complemented with RT-qPCR for target genes involved in central metabolism, signaling, and lipid biosynthesis. Using this approach dynamics in central metabolism were linked to cold-stress dependent sugar and autophagy pathways as well as novel genes in C. reinhardtii such as CKIN1, CKIN2 and a hitherto functionally not annotated protein named CKIN3. Cold stress affected extensively the physiology and the organization of the cell. Gluconeogenesis and starch biosynthesis pathways are activated leading to a pronounced starch and sugar accumulation. Quantitative lipid profiles indicate a sharp decrease in the lipophilic fraction and an increase in polyunsaturated fatty acids suggesting this as a mechanism of maintaining membrane fluidity. The proteome is completely remodeled during cold stress: specific candidates of the ribosome and the spliceosome indicate altered biosynthesis and degradation of proteins important for adaptation to low temperatures. Specific proteasome degradation may be mediated by the observed cold-specific changes in the ubiquitinylation system. Sparse partial least squares regression analysis was applied for protein correlation network analysis using proteins as predictors and Fv/Fm, FW, total lipids, and starch as responses. We applied also Granger causality analysis and revealed correlations between proteins and metabolites otherwise not detectable. Twenty percent of the proteins responsive to cold are uncharacterized proteins. This presents a considerable resource for new discoveries in cold stress biology in alga and plants.

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Adaptation to Stressors by Systemic Protein Amyloidogenesis.

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Adaptation to Stressors by Systemic Protein Amyloidogenesis.

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