TY - JOUR

T1 - Aggregation and prion-inducing properties of the g-protein gamma subunit ste18 are regulated by membrane association

AU - Chernova, Tatiana A.

AU - Yang, Zhen

AU - Karpova, Tatiana S.

AU - Shanks, John R.

AU - Shcherbik, Natalia

AU - Wilkinson, Keith D.

AU - Chernoff, Yury O.

N1 - Chernova, T.A.; Yang, Z.; Karpova, T.S.; Shanks, J.R.; Shcherbik, N.; Wilkinson, K.D.; Chernoff, Y.O. Aggregation and Prion-Inducing Properties of the G-Protein Gamma Subunit Ste18 are Regulated by Membrane Association. Int. J. Mol. Sci. 2020, 21, 5038.

PY - 2020/7/2

Y1 - 2020/7/2

N2 - Yeast prions and mnemons are respectively transmissible and non-transmissible self-perpetuating protein assemblies, frequently based on cross-β ordered detergent-resistant aggregates (amyloids). Prions cause devastating diseases in mammals and control heritable traits in yeast. It was shown that the de novo formation of the prion form [PSI+] of yeast release factor Sup35 is facilitated by aggregates of other proteins. Here we explore the mechanism of the promotion of [PSI+] formation by Ste18, an evolutionarily conserved gamma subunit of a G-protein coupled receptor, a key player in responses to extracellular stimuli. Ste18 forms detergent-resistant aggregates, some of which are colocalized with de novo generated Sup35 aggregates. Membrane association of Ste18 is required for both Ste18 aggregation and [PSI+] induction, while functional interactions involved in signal transduction are not essential for these processes. This emphasizes the significance of a specific location for the nucleation of protein aggregation. In contrast to typical prions, Ste18 aggregates do not show a pattern of heritability. Our finding that Ste18 levels are regulated by the ubiquitin-proteasome system, in conjunction with the previously reported increase in Ste18 levels upon the exposure to mating pheromone, suggests that the concentration-dependent Ste18 aggregation may mediate a mnemon-like response to physiological stimuli.

AB - Yeast prions and mnemons are respectively transmissible and non-transmissible self-perpetuating protein assemblies, frequently based on cross-β ordered detergent-resistant aggregates (amyloids). Prions cause devastating diseases in mammals and control heritable traits in yeast. It was shown that the de novo formation of the prion form [PSI+] of yeast release factor Sup35 is facilitated by aggregates of other proteins. Here we explore the mechanism of the promotion of [PSI+] formation by Ste18, an evolutionarily conserved gamma subunit of a G-protein coupled receptor, a key player in responses to extracellular stimuli. Ste18 forms detergent-resistant aggregates, some of which are colocalized with de novo generated Sup35 aggregates. Membrane association of Ste18 is required for both Ste18 aggregation and [PSI+] induction, while functional interactions involved in signal transduction are not essential for these processes. This emphasizes the significance of a specific location for the nucleation of protein aggregation. In contrast to typical prions, Ste18 aggregates do not show a pattern of heritability. Our finding that Ste18 levels are regulated by the ubiquitin-proteasome system, in conjunction with the previously reported increase in Ste18 levels upon the exposure to mating pheromone, suggests that the concentration-dependent Ste18 aggregation may mediate a mnemon-like response to physiological stimuli.

KW - Amyloid

KW - G-protein

KW - Mating

KW - Mnemon

KW - Phosphorylation

KW - Prion

KW - Ste18

KW - Sup35

KW - Ubiquitin

KW - Yeast

KW - PHOSPHORYLATION

KW - PERSISTENCE

KW - mating

KW - DUAL LIPID MODIFICATION

KW - MEMORY

KW - mnemon

KW - prion

KW - phosphorylation

KW - LOCALIZATION

KW - PSI+ PRION

KW - INVOLVEMENT

KW - SUP35

KW - ubiquitin

KW - yeast

KW - amyloid

KW - PHEROMONE RESPONSE PATHWAY

KW - YEAST PRION

UR - http://www.scopus.com/inward/record.url?scp=85088486839&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/c0a98b4b-c7b6-37f3-93ec-86825d5fc8f7/

U2 - 10.3390/ijms21145038

DO - 10.3390/ijms21145038

M3 - Article

C2 - 32708832

AN - SCOPUS:85088486839

VL - 21

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 14

M1 - 5038

ER -