A genetic approach reveals different modes of action of prefoldins

Abstract

The prefoldin complex (PFDc) was identified in humans as a co-chaperone of the cytosolic chaperonin T-COMPLEX PROTEIN RING COMPLEX (TRiC)/CHAPERONIN CONTAINING TCP-1 (CCT). PFDc is conserved in eukaryotes and is composed of subunits PFD1 to 6, and PFDc-TRiC/CCT folds actin and tubulins. PFDs also participate in a wide range of cellular processes, both in the cytoplasm and in the nucleus, and their malfunction causes developmental alterations and disease in animals and altered growth and environmental responses in yeast and plants. Genetic analyses in yeast indicate that not all their functions require the canonical complex. The lack of systematic genetic analyses in plants and animals, however, makes it difficult to discern whether PFDs participate in a process as the canonical complex or in alternative configurations, which is necessary to understand their mode of action. To tackle this question, and on the premise that the canonical complex cannot be formed if one subunit is missing, we generated an Arabidopsis (Arabidopsis thaliana) mutant deficient in the six prefoldins and compared various growth and environmental responses with those of the individual mutants. In this way, we demonstrate that the PFDc is required for seed germination, to delay flowering, or to respond to high salt stress or low temperature, whereas at least two PFDs redundantly attenuate the response to osmotic stress. A coexpression analysis of differentially expressed genes in the sextuple mutant identified several transcription factors, including ABA INSENSITIVE 5 (ABI5) and PHYTOCHROME INTERACTING FACTOR 4 (PIF4), acting downstream of PFDs. Furthermore, the transcriptomic analysis allowed assigning additional roles for PFDs, for instance, in response to higher temperature.

The unconventional prefoldin RPB5 interactor mediates the gravitropic response by modulating cytoskeleton organization and auxin transport in Arabidopsis

“…Prefoldin is involved in actin and tubulin stability in eukaryotes (Martin‐Benito et al, 2002; Wang et al, 2015). In Arabidopsis , all PFDs contribute to microtubule dynamics and organization (Gu et al, 2008; Rodriguez‐Milla and Salinas, 2009; Perea‐Resa et al, 2017; Blanco‐Touriñán et al, 2021). Since AtURI can interact with PFD2 and PFD6, it is possible that the actin and/or tubulin networks are altered in the aturi‐1 mutant.…”

“…In the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster , PFD‐deficient cells show low tubulin levels and several cytoskeleton abnormalities (Lundin et al, 2008; Delgehyr et al, 2012). In Arabidopsis , all PFD members participate in microtubule dynamic organization and pfd mutants exhibit impaired cell elongation and division (Gu et al, 2008; Rodriguez‐Milla and Salinas, 2009; Perea‐Resa et al, 2017; Blanco‐Touriñán et al, 2021). Besides their concerted role in the PFD complex, individual subunits may affect abiotic stress responses or contribute to gene expression (Blanco‐Touriñán et al, 2021).…”

“…In Arabidopsis , all PFD members participate in microtubule dynamic organization and pfd mutants exhibit impaired cell elongation and division (Gu et al, 2008; Rodriguez‐Milla and Salinas, 2009; Perea‐Resa et al, 2017; Blanco‐Touriñán et al, 2021). Besides their concerted role in the PFD complex, individual subunits may affect abiotic stress responses or contribute to gene expression (Blanco‐Touriñán et al, 2021). Unconventional prefoldin RPB5 interactor (URI) is another unconventional prefoldin that contains an α‐type prefoldin, RPB5 (RNA polymerase II subunit 5) binding domain and a URI box (Gstaiger et al, 2003; Delgermaa et al, 2004; Miron‐Garcia et al, 2013).…”

Prefoldin Function in Cellular Protein Homeostasis and Human Diseases

“…A mutant of Arabidopsis that harbored deletions of all six prefoldin subunits was viable, and loss of the prefoldin complex did not significantly alter plant development under normal growth conditions. The prefoldin complex knockout mutant performed better than the wild type under osmotic stress conditions ( Blanco-Touriñán et al, 2021 ). This indicates that prefoldin is needed to respond to stress conditions and/or environmental changes.…”

Fine-Tuning Cold Stress Response Through Regulated Cellular Abundance and Mechanistic Actions of Transcription Factors

“…Interestingly, the study showed that degradation of HY5 occurred in COP1-independent manner ( Perea-Resa et al, 2017 ). Based on the findings, it is anticipated that prefoldin contributes indirectly through participation in cellular proteostasis to regulate the stability of TFs or complexes involved in different stages of gene expression ( Blanco-Touriñán et al, 2021 ). Figure 2 provides a schematic diagram on translational and post-translational modifications affecting CBF-dependent signaling for cold acclimation that has been discussed.…”