All Publications


  • Effects of stress-induced increases of corticosterone on circulating triglyceride levels, biliverdin concentration, and heme oxygenase expression COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY Butler, M. W., Armour, E. M., Minnick, J. A., Rossi, M. L., Schock, S. F., Berger, S. E., Hines, J. K. 2020; 240: 110608

    Abstract

    When exposed to stressors, animals physiologically respond by secreting glucocorticoid hormones. Most birds, reptiles, and amphibians secrete corticosterone (CORT), which allows them to maximize short-term survival, including by modulating lipid metabolism. However, the factors regulating lipid metabolism, particularly during acute (i.e., short-term) stressors, are not well-characterized. To investigate one putative mechanism, we examined how expression of the enzyme heme oxygenase (HO), which primarily converts heme into biliverdin, changes during an acute stressor. Because HO has links to decreased levels of triglycerides, we tested the hypothesis that an acute stressor increases HO expression, which would concomitantly decrease circulating lipid levels. We compared free-living house sparrow (Passer domesticus) nestlings exposed to a one-hour stressor to control individuals, and quantified HO expression and biliverdin concentration in spleen, liver, or kidney tissue, as well as circulating CORT, triglyceride, and glycerol levels. Nestlings exposed to a stressor had reduced circulating triglycerides consistent with an increased rate of gluconeogenesis during an acute stressor. Concentrations of triglycerides were also negatively correlated with HO expression in the liver, which is consistent with mammalian studies. However, contrary to our predictions, exposure to a stressor did not affect HO expression, or biliverdin concentration in liver, spleen, or kidney. Overall, our results support links between CORT, triglyceride levels, and HO expression, though the molecular pathways connecting these metrics still need to be elucidated.

    View details for DOI 10.1016/j.cbpa.2019.110608

    View details for Web of Science ID 000508489600012

    View details for PubMedID 31704186

  • Three J-proteins impact Hsp104-mediated variant-specific prion elimination: a new critical role for a low-complexity domain CURRENT GENETICS Berger, S. E., Nolte, A. M., Kamiya, E., Hines, J. K. 2020; 66 (1): 51–58

    Abstract

    Prions are self-propagating protein isoforms that are typically amyloid. In Saccharomyces cerevisiae, amyloid prion aggregates are fragmented by a trio involving three classes of chaperone proteins: Hsp40s, also known as J-proteins, Hsp70s, and Hsp104. Hsp104, the sole Hsp100-class disaggregase in yeast, along with the Hsp70 Ssa and the J-protein Sis1, is required for the propagation of all known amyloid yeast prions. However, when Hsp104 is ectopically overexpressed, only the prion [PSI+] is efficiently eliminated from cell populations via a highly debated mechanism that also requires Sis1. Recently, we reported roles for two additional J-proteins, Apj1 and Ydj1, in this process. Deletion of Apj1, a J-protein involved in the degradation of sumoylated proteins, partially blocks Hsp104-mediated [PSI+] elimination. Apj1 and Sis1 were found to have overlapping functions, as overexpression of one compensates for loss of function of the other. In addition, overexpression of Ydj1, the most abundant J-protein in the yeast cytosol, completely blocks Hsp104-mediated curing. Yeast prions exhibit structural polymorphisms known as "variants"; most intriguingly, these J-protein effects were only observed for strong variants, suggesting variant-specific mechanisms. Here, we review these results and present new data resolving the domains of Apj1 responsible, specifically implicating the involvement of Apj1's Q/S-rich low-complexity domain.

    View details for DOI 10.1007/s00294-019-01006-5

    View details for Web of Science ID 000513356600005

    View details for PubMedID 31230108

    View details for PubMedCentralID PMC6925661

  • Variant-specific and reciprocal Hsp40 functions in Hsp104-mediated prion elimination MOLECULAR MICROBIOLOGY Astor, M. T., Kamiya, E., Sporn, Z. A., Berger, S. E., Hines, J. K. 2018; 109 (1): 41–62

    Abstract

    The amyloid-based prions of Saccharomyces cerevisiae are heritable aggregates of misfolded proteins, passed to daughter cells following fragmentation by molecular chaperones including the J-protein Sis1, Hsp70 and Hsp104. Overexpression of Hsp104 efficiently cures cell populations of the prion [PSI+ ] by an alternative Sis1-dependent mechanism that is currently the subject of significant debate. Here, we broadly investigate the role of J-proteins in this process by determining the impact of amyloid polymorphisms (prion variants) on the ability of well-studied Sis1 constructs to compensate for Sis1 and ask whether any other S. cerevisiae cytosolic J-proteins are also required for this process. Our comprehensive screen, examining all 13 members of the yeast cytosolic/nuclear J-protein complement, uncovered significant variant-dependent genetic evidence for a role of Apj1 (antiprion DnaJ) in this process. For strong, but not weak [PSI+ ] variants, depletion of Apj1 inhibits Hsp104-mediated curing. Overexpression of either Apj1 or Sis1 enhances curing, while overexpression of Ydj1 completely blocks it. We also demonstrated that Sis1 was the only J-protein necessary for the propagation of at least two weak [PSI+ ] variants and no J-protein alteration, or even combination of alterations, affected the curing of weak [PSI+ ] variants, suggesting the possibility of biochemically distinct, variant-specific Hsp104-mediated curing mechanisms.

    View details for DOI 10.1111/mmi.13966

    View details for Web of Science ID 000438902600003

    View details for PubMedID 29633387

    View details for PubMedCentralID PMC6099457