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This article is a Commentary on Wang et al., 216: 205–215.

This chapter contains sections titled: Introduction The Basis and Basics of Plant‐Pathogen Coevolution Oomycete MAMPs: Activating the Frontline of Plant Defense The Expanding Oomycete Effector Collection: Suppressors of PTI and Manipulators of Host Metabolism Cytoplasmic Effectors ETI to Oomycete Plant Pathogens Biotrophy versus Necrotrophy: Genome Studies Reveal the Differences The Future: From Systems Biology to Translational Research

The antimicrobial functions of neutrophils are facilitated by a defensive armamentarium of proteins stored in granules, and by the formation of neutrophil extracellular traps (NETs). However, the toxic nature of these structures poses a threat to highly vascularized tissues, such as the lungs. Here, we identified a cell-intrinsic program that modified the neutrophil proteome in the circulation and caused the progressive loss of granule content and reduction of the NET-forming capacity. This program was driven by the receptor CXCR2 and by regulators of circadian cycles. As a consequence, lungs were protected from inflammatory injury at times of day or in mouse mutants in which granule content was low. Changes in the proteome, granule content and NET formation also occurred in human neutrophils, and correlated with the incidence and severity of respiratory distress in pneumonia patients. Our findings unveil a ‘disarming’ strategy of neutrophils that depletes protein stores to reduce the magnitude of inflammation. Hidalgo and colleagues describe a cell-intrinsic program that induces changes in the proteome, granule content and NET-forming capacity of neutrophils and is driven by the chemokine receptor CXCR2 and regulators of the circadian clock.

Cytoplasmic dynein is the major minus-end-directed microtubule-based motor in cells. Dynein processivity and cargo selectivity depend on cargo-specific effectors that, while generally unrelated, share the ability to interact with dynein and dynactin to form processive dynein–dynactin-effector complexes. How this is achieved is poorly understood. Here, we identify a conserved region of the dynein Light Intermediate Chain 1 (LIC1) that mediates interactions with unrelated dynein–dynactin effectors. Quantitative binding studies map these interactions to a conserved helix within LIC1 and to N-terminal fragments of Hook1, Hook3, BICD2, and Spindly. A structure of the LIC1 helix bound to the N-terminal Hook domain reveals a conformational change that creates a hydrophobic cleft for binding of the LIC1 helix. The LIC1 helix competitively inhibits processive dynein–dynactin-effector motility in vitro, whereas structure-inspired mutations in this helix impair lysosomal positioning in cells. The results reveal a conserved mechanism of effector interaction with dynein–dynactin necessary for processive motility. A growing number of cargo-specific effector proteins are being identified that interact with both dynein and dynactin and form processive dynein-dynactin-effector complexes. Here the authors identify and characterize a conserved mechanism of interaction between dynein and unrelated effector proteins.

The active transport of organelles and other cargos along the axon is required to maintain neuronal health and function, but we are just beginning to understand the complex regulatory mechanisms involved. The molecular motors, cytoplasmic dynein and kinesins, transport cargos along microtubules; this transport is tightly regulated by adaptors and effectors. Here we review our current understanding of motor regulation in axonal transport. We discuss the mechanisms by which regulatory proteins induce or repress the activity of dynein or kinesin motors, and explore how this regulation plays out during organelle trafficking in the axon, where motor activity is both cargo specific and dependent on subaxonal location. We survey several well-characterized examples of membranous organelles subject to axonal transport — including autophagosomes, endolysosomes, signalling endosomes, mitochondria and synaptic vesicle precursors — and highlight the specific mechanisms that regulate motor activity to provide localized trafficking within the neuron. Defects in axonal transport have been implicated in conditions ranging from developmental defects in the brain to neurodegenerative disease. Better understanding of the underlying mechanisms will be essential to develop more-effective treatment options.Homeostasis and function of neurons rely on long-distance, bidirectional microtubule-based transport along the axon, which is driven by both dynein and kinesin motors. How these motors are regulated by a plethora of adaptors and effectors to ensure appropriate and robust distribution of cargos is an area of intense study.

ABSTRACT Receptor-like cytoplasmic kinases (RLCKs) play crucial roles in regulating plant development and immunity. Conserved pathogen-associated molecular patterns (PAMPs) derived from microbes are recognized by plant pattern recognition receptors to activate PAMP-triggered immunity (PTI). Microbial effectors, whose initial function is to promote virulence, are recognized by plant intracellular nucleotide-binding domain and leucine-rich repeat receptors (NLRs) to initiate effector-triggered immunity (ETI). Both PTI and ETI trigger early immune signaling events including the production of reactive oxygen species, induction of calcium influx and activation of mitogen-activated protein kinases. Research progress has revealed the important roles of RLCKs in the regulation of early PTI signaling. Accordingly, RLCKs are often targeted by microbial effectors that are evolved to evade PTI via diverse modulations. In some cases, modulation of RLCKs by microbial effectors triggers the activation of NLRs. This review covers the mechanisms by which RLCKs engage diverse substrates to regulate early PTI signaling and the regulatory roles of RLCKs in triggering NLR activation. Accumulating evidence suggests evolutionary links and close connections between PAMP- and effector-triggered early immune signaling that are mediated by RLCKs. As key immune regulators, RLCKs can be considered targets with broad prospects for the improvement of plant resistance via genetic engineering. Receptor-like cytoplasmic kinases play important roles in the regulation of plant PRR-mediated early immune signaling and NLR activation.

Plant pathogens use effector proteins to target host processes involved in pathogen perception, immune signalling, or defence outputs. Unlike foliar pathogens, it is poorly understood how root‐invading pathogens suppress immunity. The Avr2 effector from the tomato root‐ and xylem‐colonizing pathogen Fusarium oxysporum suppresses immune signalling induced by various pathogen‐associated molecular patterns (PAMPs). It is unknown how Avr2 targets the immune system. Transgenic AVR2 Arabidopsis thaliana phenocopies mutants in which the pattern recognition receptor (PRR) co‐receptor BRI1‐ASSOCIATED RECEPTOR KINASE (BAK1) or its downstream signalling kinase BOTRYTIS‐INDUCED KINASE 1 (BIK1) are knocked out. We therefore tested whether these kinases are Avr2 targets. Flg22‐induced complex formation of the PRR FLAGELLIN SENSITIVE 2 and BAK1 occurred in the presence and absence of Avr2, indicating that Avr2 does not affect BAK1 function or PRR complex formation. Bimolecular fluorescence complementation assays showed that Avr2 and BIK1 co‐localize in planta. Although Avr2 did not affect flg22‐induced BIK1 phosphorylation, mono‐ubiquitination was compromised. Furthermore, Avr2 affected BIK1 abundance and shifted its localization from nucleocytoplasmic to the cell periphery/plasma membrane. Together, these data imply that Avr2 may retain BIK1 at the plasma membrane, thereby suppressing its ability to activate immune signalling. Because mono‐ubiquitination of BIK1 is required for its internalization, interference with this process by Avr2 could provide a mechanistic explanation for the compromised BIK1 mobility upon flg22 treatment. The identification of BIK1 as an effector target of a root‐invading vascular pathogen identifies this kinase as a conserved signalling component for both root and shoot immunity. Avr2 from Fusarium oxysporum co‐localizes with BIK1 and affects flg22‐induced mono‐ubiquitination, membrane dissociation and protein accumulation, but not phosphorylation of the signalling kinase.

Citrus Huanglongbing (HLB), known as the most economically devastating disease in citrus industry, is mainly caused by phloem-restricted Gram-negative bacterium “ Candidatus Liberibacter asiaticus” ( C Las). To date, C Las is still unculturable in vitro , which has been dramatically delaying the research on its pathogenesis, and only few Sec-dependent effectors (SDEs) have been identified to elucidate the pathogenesis of C Las. Here, we confirmed that a C Las-secreted Sec-dependent polypeptide, namely SECP8 (CLIBASIA_05330), localized in nucleus, cytoplasm and cytoplasmic membrane, and showed remarkably higher transcript abundance in citrus than in psyllids. Potato virus X (PVX)-mediated transient expression assays indicated that mSECP8 (the mature form of SECP8) suppressed pro-apoptotic mouse protein BAX and Phytophthora infestans elicitin INF1-triggered hypersensitive response (HR) associated phenotypes, including cell death, H 2 O 2 accumulation and callose deposition. Intriguingly, mSECP8 also inhibited SDE1 (CLIBASIA_05315)-induced water-soaked and dwarfing symptoms in Nicotiana benthamiana . In addition, mSECP8 can promote the susceptibility of transgenic Wanjincheng orange ( Citrus sinensis ) to C Las invasion and further HLB symptom development, and it contributes to the proliferation of Xanthomonas citri subsp. citri ( Xcc ). Moreover, the expression of ten immunity-related genes were significantly down-regulated in mSECP8 transgenic citrus than those in wide-type (WT) plants. Overall, we propose that mSECP8 may serve as a novel broad-spectrum suppressor of plant immunity, and provide the first evidence counteractive effect among C Las effectors. This study will enrich and provide new evidences for elucidating the pathogenic mechanisms of C Las in citrus host.

Sequence-specific nucleases are commonly used to modify the nuclear genome of plants. However, targeted modification of the mitochondrial genome of land plants has not yet been achieved. In plants, a type of male sterility called cytoplasmic male sterility (CMS) has been attributed to certain mitochondrial genes, but none of these genes has been validated by direct mitochondrial gene-targeted modification. Here, we knocked out CMS-associated genes ( orf79 and orf125 ) of CMS varieties of rice and rapeseed, respectively, using transcription activator-like effector nucleases (TALENs) with mitochondria localization signals (mitoTALENs). We demonstrate that knocking out these genes cures male sterility, strongly suggesting that these genes are causes of CMS. Sequencing revealed that double-strand breaks induced by mitoTALENs were repaired by homologous recombination, and that during this process, the target genes and surrounding sequences were deleted. Our results show that mitoTALENs can be used to stably and heritably modify the mitochondrial genome in plants. Knockout of cytoplasmic male-sterility-associated genes using TALENs with mitochondria localization signals rescues male sterility in rice and rapeseed, validating the role of these genes, and provides a method for plant mitochondrial genome editing.

Background Effector memory T cells are pivotal effectors of adaptive immunity with enhanced migration characteristics and are involved in the pathogenesis of ANCA-associated vasculitis (AAV). The diversity of effector memory T cells in chemokine receptor expression has been well studied in proteinase 3 (PR3)-AAV. However, few studies have been conducted in myeloperoxidase (MPO)-AAV. Here, we characterized chemokine receptor expression on effector memory T cells from patients with active MPO-AAV. Methods Clinical data from newly diagnosed MPO-AAV patients and healthy subjects were collected and analyzed. Human peripheral blood mononuclear cells (PBMCs) isolated from patients with active MPO-AAV were analyzed by flow cytometry. The production of effector memory T cell-related chemokines in serum was assessed by ELISA. Results We observed decreased percentages of CD4 + and CD8 + T cells in the peripheral blood, accompanied by a significant decrease in CCR6-expressing T cells but an increase in CXCR3 + T cells, in active MPO-AAV. Furthermore, the decrease in CCR6 and increase in CXCR3 expression were mainly limited to effector memory T cells. Consistent with this finding, the serum level of CCL20 was increased. In addition, a decreasing trend in the T EM 17 cell frequency, with concomitant increases in the frequencies of CD4 + T EM 1 and CD4 + T EM 17.1 cells, was observed when T cell functional subsets were defined by chemokine receptor expression. Moreover, the proportions of peripheral CD8 + T cells and CD4 + T EM subsets were correlated with renal prognosis and inflammatory markers. Conclusions Our data indicate that dysregulated chemokine receptor expression on CD4 + and CD8 + effector memory T cells and aberrant distribution of functional CD4 + T cell subsets in patients with active MPO-AAV have critical roles related to kidney survival.