Ubiquitination of Receptorsomes, Frontline of Plant Immunity

Abstract

Sessile plants are constantly exposed to myriads of unfavorable invading organisms with different lifestyles. To survive, plants have evolved plasma membrane-resident pattern recognition receptors (PRRs) and intracellular nucleotide-binding domain leucine-rich repeat receptors (NLRs) to initiate sophisticated downstream immune responses. Ubiquitination serves as one of the most important and prevalent posttranslational modifications (PTMs) to fine-tune plant immune responses. Over the last decade, remarkable progress has been made in delineating the critical roles of ubiquitination in plant immunity. In this review, we highlight recent advances in the understanding of ubiquitination in the modulation of plant immunity, with a particular focus on ubiquitination in the regulation of receptorsomes, and discuss how ubiquitination and other PTMs act in concert to ensure rapid, proper, and robust immune responses.

Keywords: plant immunity; posttranslational modifications (PTMs); receptorsomes; ubiquitination.

Figure 1

Ubiquitination regulation of PRR receptorsome-mediated signaling in Arabidopsis. In the resting state, exocyst subunits EXO70B1/2 regulate trafficking of the bacterial flagellin receptor FLS2 to the plasma membrane (PM). FLS2 associates with non-activated RLCK BIK1 subjected to polyubiquitination regulation by the E3 ligases PUB25/26. CPK28 phosphorylates PUB25/26 and enhances their enzymatic activities. In parallel, the protein abundance of the fungal chitin receptor LYK5 is also regulated by PUB13. The Raf-like MAPKKK family member EDR1 associates with and negatively affects KEG phosphorylation and self-ubiquitination, thereby enhancing MKK4/5 ubiquitination mediated by KEG. In addition, another E3 ligase, PUB22, undergoes degradation by autoubiquitination in a resting state. Upon flagellin perception by its cognate PRR FLS2, BAK1 phosphorylates PUB12/13, which promotes PUB12/13-targeting-activated FLS2, leading to polyubiquitination and degradation. E2 UBC8 partners with PUB13 and mediates FLS2 polyubiquitination. In contrast, chitin induces the dissociation of PUB13 and LYK5, thus reducing LYK5 polyubiquitination and promoting LYK5 protein accumulation. PUB4 is phosphorylated by CERK1 and positively regulates chitin signaling. Unlike the polyubiquitination of BIK1 in a resting state, flg22-induced BIK1 activation requires E3 ligase RH3A/3B-mediated monoubiquitination. In addition, E3 ligases ATL31/6 positively regulate BIK1-mediated immunity by targeting CPK28 for ubiquitination and relief of the CPK28-mediated negative regulation of BIK1. Additionally, PUB22 is stabilized upon flg22 perception by inhibiting the autoubiquitination activity and oligomerization of flg22, which dampens the immune responses by promoting the ubiquitination of EXO70B2 and its degradation via the 26 S proteasome. Bacteria-delivered AvrPtoB ubiquitinates EXO70B1, leading to degradation and thereby suppressing immune responses. In addition, AvrPtoB targets multiple PRRs, including FLS2, CERK1, and LecRK-IX.2, for ubiquitination, thereby suppressing the response of PTI. In turn, PTI activation facilitates LecRK-IX.2 to phosphorylate AvrPtoB, which disrupts the self-association and compromises the virulence of AvrPtoB.

Figure 2

A working model of the ubiquitination regulation of NLR homeostasis. Under normal conditions, a potential unknown substrate is ubiquitinated by the E3 ligase SAUL1, which leads to the degradation of SAUL1′s substrate and deactivates PTI. In addition, SAUL1 associates with the NLR pairs SOC3–CHS1 and is required for SOC3-mediated immune activation. Another E3 ligase, SCFCPR1, interacts with SNC1, RPS2, and SUMM2 and contributes to their ubiquitination and degradation. The TRAF protein MUSE13 homodimerizes and heterodimerizes with NLRs and SCFCPR1 to facilitate SNC1 and RPS2 turnover. The E4 ligase MUSE3 associates with SNC1 and promotes efficient elongation of the ubiquitin chain in NLRs. AAA–ATPase CDC48A interacts with MUSE3 and contributes to the NLR polyubiquitination process. In contrast, the SCFSNIPER7 complex regulates unfoldase CDC48A protein turnover and modulates immune output. MEKK2 scaffolds RLK LET1, which stabilizes SUMM2, and counter-regulates SCFCPR1-mediated SUMM2 ubiquitination. SNIPER1 and its homolog SNIPER2 globally control the protein levels of sNLRs for the immediate attenuation of immune output to effectively avoid autoimmunity. When plants are challenged with an incompatible pathogen carrying an unknown effector that specifically targets SAUL1, SAUL1 is inactivated, leading to the accumulation of the SAUL substrate, which represses PTI. Meanwhile, the inactivation of SAUL1 results in the constitutive activation of SOC3, triggering strong ETI. The effectors induce MEKK1–MKK1/MKK2–MPK4 cascade activation. However, some effectors may disrupt the MEKK1–MKK1/MKK2–MPK4 cascade, leading to CNL SUMM2 and TNL RPS6 activation and intensive activation of the ETI response.