Insights into prion biology: Integrating a protein misfolding pathway with its cellular environment

Susanne DiSalvo, Tricia R Serio

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Protein misfolding and assembly into ordered, self-templating aggregates (amyloid) has emerged as a novel mechanism for regulating protein function. For a subclass of amyloidogenic proteins known as prions, this process induces transmissible changes in normal cellular physiology, ranging from neurodegenerative disease in animals and humans to new traits in fungi. The severity and stability of these altered phenotypic states can be attenuated by the conformation or amino-acid sequence of the prion, but in most of these cases, the protein retains the ability to form amyloid in vitro. Thus, our ability to link amyloid formation in vitro with its biological consequences in vivo remains a challenge. In two recent studies, we have begun to address this disconnect by assessing the effects of the cellular environment on traits associated with the misfolding of the yeast prion Sup35. Remarkably, the effects of quality control pathways and of limitations on protein transfer in vivo amplify the effects of even slight differences in the efficiency of Sup35 misfolding, leading to dramatic changes in the associated phenotype. Together, our studies suggest that the interplay between protein misfolding pathways and their cellular context is a crucial contributor to prion biology.

Original languageEnglish (US)
Pages (from-to)76-83
Number of pages8
JournalPrion
Volume5
Issue number2
DOIs
StatePublished - Apr 2011
Externally publishedYes

Fingerprint

Prions
Amyloid
Proteins
Neurodegenerative diseases
Amyloidogenic Proteins
Physiology
Fungi
Neurodegenerative Diseases
Quality Control
Yeast
Quality control
Conformations
Amino Acid Sequence
Animals
Yeasts
Phenotype
Amino Acids
In Vitro Techniques

Keywords

  • Aggregate size
  • Amyloid
  • Chaperones
  • Hsp104
  • Ordered aggregates
  • Prion
  • Protein misfolding
  • Sup35
  • Transmission

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Infectious Diseases
  • Cellular and Molecular Neuroscience

Cite this

Insights into prion biology : Integrating a protein misfolding pathway with its cellular environment. / DiSalvo, Susanne; Serio, Tricia R.

In: Prion, Vol. 5, No. 2, 04.2011, p. 76-83.

Research output: Contribution to journalArticle

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