title: Targeted degradation of abscisic acid receptors is mediated by the ubiquitin ligase substrate adaptor DDA1 in Arabidopsis.
abstract: CULLIN4-RING E3 ubiquitin ligases (CRL4s) regulate key developmental and stress responses in eukaryotes. Studies in both animals and plants have led to the identification of many CRL4 targets as well as specific regulatory mechanisms that modulate their function. The latter involve COP10-DET1-DDB1 (CDD)-related complexes, which have been proposed to facilitate target recognition by CRL4, although the molecular basis for this activity remains largely unknown. Here, we provide evidence that Arabidopsis thaliana DET1-, DDB1-ASSOCIATED1 (DDA1), as part of the CDD complex, provides substrate specificity for CRL4 by interacting with ubiquitination targets. Thus, we show that DDA1 binds to the abscisic acid (ABA) receptor PYL8, as well as PYL4 and PYL9, in vivo and facilitates its proteasomal degradation. Accordingly, we found that DDA1 negatively regulates ABA-mediated developmental responses, including inhibition of seed germination, seedling establishment, and root growth. All other CDD components displayed a similar regulatory function, although they did not directly interact with PYL8. Interestingly, DDA1-mediated destabilization of PYL8 is counteracted by ABA, which protects PYL8 by limiting its polyubiquitination. Altogether, our data establish a function for DDA1 as a substrate receptor for CRL4-CDD complexes and uncover a mechanism for the desensitization of ABA signaling based on the regulation of ABA receptor stability.
authors.affiliation: Centro Nacional de Biotecnología-Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Irigoyen
authors.forename: Elisa
authors.initials: E
authors.lastname: Iniesto
authors.forename: Lesia
authors.initials: L
authors.lastname: Rodriguez
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Puga
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yanagawa
authors.forename: Elah
authors.initials: E
authors.lastname: Pick
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Strickland
authors.forename: Javier
authors.initials: J
authors.lastname: Paz-Ares
authors.forename: Ning
authors.initials: N
authors.lastname: Wei
authors.forename: Geert
authors.initials: G
authors.lastname: De Jaeger
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Rodriguez
authors.forename: Xing Wang
authors.initials: XW
authors.lastname: Deng
authors.forename: Vicente
authors.initials: V
authors.lastname: Rubio
mesh_terms: D000040:Abscisic Acid / Q000378:metabolism* / Q000494:pharmacology; D017360:Arabidopsis / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D029681:Arabidopsis Proteins / Q000378:metabolism*; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D025821:Polyubiquitin / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013379:Substrate Specificity / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D029681:Arabidopsis Proteins; C000592956:DDA1 (DDB1-ASSOCIATED1) protein, Arabidopsis; D046912:Multiprotein Complexes; D011956:Receptors, Cell Surface; D025821:Polyubiquitin; D000040:Abscisic Acid; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex