Functional role of Tia1/Pub1 and Sup35 prion domains: directing protein synthesis machinery to the tubulin cytoskeleton

Xiang Li; Joseph B Rayman; Eric R Kandel; Irina L Derkatch

doi:10.1016/j.molcel.2014.05.027

Functional role of Tia1/Pub1 and Sup35 prion domains: directing protein synthesis machinery to the tubulin cytoskeleton

Mol Cell. 2014 Jul 17;55(2):305-18. doi: 10.1016/j.molcel.2014.05.027. Epub 2014 Jun 26.

Authors

Xiang Li¹, Joseph B Rayman¹, Eric R Kandel², Irina L Derkatch³

Affiliations

¹ Department of Neuroscience, College of Physicians and Surgeons of Columbia University, 645 Kolb Research Annex, 1051 Riverside Drive, New York, NY 10032, USA.
² Department of Neuroscience, College of Physicians and Surgeons of Columbia University, 645 Kolb Research Annex, 1051 Riverside Drive, New York, NY 10032, USA; Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York, NY 10032, USA; Kavli Institute for Brain Science, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA; Howard Hughes Medical Institute, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. Electronic address: erk5@columbia.edu.
³ Department of Neuroscience, College of Physicians and Surgeons of Columbia University, 645 Kolb Research Annex, 1051 Riverside Drive, New York, NY 10032, USA. Electronic address: irina.derkatch@gmail.com.

Abstract

Tia1/Pub1 is a stress granule component carrying a Q/N-rich prion domain. We provide direct evidence that Tia1 forms a prion in yeast. Moreover, Tia1/Pub1 acts cooperatively with release factor Sup35/eRF3 to establish a two-protein self-propagating state. This two-protein prion driven by the Q/N-rich prion domains of Sup35 and Tia1/Pub1 can be visualized as distinctive line structures along tubulin cytoskeleton. Furthermore, we find that tubulin-associated complex containing Pub1 and Sup35 oligomers normally exists in yeast, and its assembly depends on prion domains of Pub1 and Sup35. This Sup35/Pub1 complex, which also contains TUB1 mRNA and components of translation machinery, is important for the integrity of the tubulin cytoskeleton: PUB1 disruption and Sup35 depletion from the complex lead to cytoskeletal defects. We propose that the complex is implicated in protein synthesis at the site of microtubule assembly. Thus our study identifies the role for prion domains in the assembly of multiprotein complexes.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amyloid / metabolism
Animals
Cytoskeleton / metabolism*
Mice
Mice, Inbred C57BL
Peptide Termination Factors / chemistry
Peptide Termination Factors / metabolism*
Poly(A)-Binding Proteins / chemistry
Poly(A)-Binding Proteins / metabolism*
Prions / chemistry
Prions / metabolism*
Protein Biosynthesis
Protein Multimerization
Protein Structure, Tertiary
RNA, Fungal / metabolism
RNA, Messenger / metabolism
RNA-Binding Proteins / chemistry
RNA-Binding Proteins / metabolism*
Recombinant Proteins / chemistry
Recombinant Proteins / metabolism
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / chemistry
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*
T-Cell Intracellular Antigen-1

Substances

Amyloid
PUB1 protein, S cerevisiae
Peptide Termination Factors
Poly(A)-Binding Proteins
Prions
RNA, Fungal
RNA, Messenger
RNA-Binding Proteins
Recombinant Proteins
SUP35 protein, S cerevisiae
Saccharomyces cerevisiae Proteins
T-Cell Intracellular Antigen-1
Tia1 protein, mouse
Tub1 protein, S cerevisiae
peptide-chain-release factor 3

Abstract

Publication types

MeSH terms

Substances

Grants and funding