Efficient chaperone-mediated tubulin biogenesis is essential for cell division and cell migration in C. elegans.
The efficient folding of actin and tubulin in vitro and in Saccharomyces cerevisiae is known to require the molecular chaperones prefoldin and CCT, yet little is known about the functions of these chaperones in multicellular organisms. Whereas none of the six prefoldin genes are essential in yeast, where prefoldin-independent folding of actin and tubulin is sufficient for viability, we demonstrate that reducing prefoldin function by RNAi in Caenorhabditis elegans causes defects in cell division that result in embryonic lethality. Our analyses suggest that these defects result mainly from a decrease in alpha-tubulin levels and a subsequent reduction in the microtubule growth rate. Prefoldin subunit 1 (pfd-1) mutant animals with maternally contributed PFD-1 develop to the L4 larval stage with gonadogenesis defects that include aberrant distal tip cell migration. Importantly, RNAi knockdown of prefoldin, CCT or tubulin in developing animals phenocopy the pfd-1 cell migration phenotype. Furthermore, reducing CCT function causes more severe phenotypes (compared with prefoldin knockdown) in the embryo and developing gonad, consistent with a broader role for CCT in protein folding. Overall, our results suggest that efficient chaperone-mediated tubulin biogenesis is essential in C. elegans, owing to the critical role of the microtubule cytoskeleton in metazoan development.
Lundin
Victor F
VF
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, Canada.
Srayko
Martin
M
Hyman
Anthony A
AA
Leroux
Michel R
MR
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002455:Cell Division; D002465:Cell Movement; D018385:Centrosome; D048749:Cytokinesis; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism*; D008540:Meiosis; D008870:Microtubules / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D018832:Molecular Chaperones; D014404:Tubulin; C112806:prefoldin