Functional interaction between phosducin-like protein 2 and cytosolic chaperonin is essential for cytoskeletal protein function and cell cycle progression

Peter C Stirling; Martin Srayko; Karam S Takhar; Andrei Pozniakovsky; Anthony A Hyman; Michel R Leroux

doi:10.1091/mbc.e07-01-0069

Functional interaction between phosducin-like protein 2 and cytosolic chaperonin is essential for cytoskeletal protein function and cell cycle progression

Mol Biol Cell. 2007 Jun;18(6):2336-45. doi: 10.1091/mbc.e07-01-0069. Epub 2007 Apr 11.

Authors

Peter C Stirling¹, Martin Srayko, Karam S Takhar, Andrei Pozniakovsky, Anthony A Hyman, Michel R Leroux

Affiliation

¹ Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.

Abstract

The Chaperonin Containing Tcp1 (CCT) maintains cellular protein folding homeostasis in the eukaryotic cytosol by assisting the biogenesis of many proteins, including actins, tubulins, and regulators of the cell cycle. Here, we demonstrate that the essential and conserved eukaryotic phosducin-like protein 2 (PhLP2/PLP2) physically interacts with CCT and modulates its folding activity. Consistent with this functional interaction, temperature-sensitive alleles of Saccharomyces cerevisiae PLP2 exhibit cytoskeletal and cell cycle defects. We uncovered several high-copy suppressors of the plp2 alleles, all of which are associated with G1/S cell cycle progression but which do not appreciably affect cytoskeletal protein function or fully rescue the growth defects. Our data support a model in which Plp2p modulates the biogenesis of several CCT substrates relating to cell cycle and cytoskeletal function, which together contribute to the essential function of PLP2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / metabolism
Alleles
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Cell Cycle / physiology*
Cell Nucleus / metabolism
Chaperonin Containing TCP-1
Chaperonins / genetics
Chaperonins / metabolism*
Cytoskeletal Proteins / genetics
Cytoskeletal Proteins / metabolism*
Cytoskeleton / metabolism*
GTP-Binding Proteins / metabolism
Humans
Microtubules / metabolism
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Phenotype
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Saccharomyces cerevisiae / cytology
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*
Temperature

Substances

Actins
Carrier Proteins
Cytoskeletal Proteins
Nerve Tissue Proteins
PDCL2 protein, human
Recombinant Fusion Proteins
Saccharomyces cerevisiae Proteins
TCP1 protein, human
phosducin-like protein 2, S cerevisiae
Chaperonin Containing TCP-1
Chaperonins
GTP-Binding Proteins