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Arabidopsis CALMODULIN-BINDING PROTEIN 60b plays dual roles in plant immunity

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Plant Communications 2021年第6期2卷 1-11页

作者： Weijie Huang Zhongshou Wu Hainan Tian Xin Li Yuelin Zhang Department of Botany University of British ColumbiaVancouverBC V6T 1Z4Canada michael smith laboratories University of British ColumbiaVancouverBC V6T 1Z4Canada

Arabidopsis SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1(SARD1)and CALMODULIN-BINDING PROTEIN 60g(CBP60g)are two master transcription factors that regulate many defense-related genes in plant immunity.They are required for immunity downstream of the receptor-like protein SUPPRESSOR OF NPR1-1,CONSTITUTIVE 2(SNC2).Constitutive defense responses in the gain-of-function autoimmune snc2-1D mutant are modestly affected in either sard1 or cbp60g single mutants but completely suppressed in the sard1 cbp60g double mutant.Here we report that CBP60b,another member of the CBP60 family,also functions as a positive regulator of SNC2-mediated immunity.Loss-of-function mutations of CBP60b suppress the constitutive expression of SARD1 and enhanced disease resistance in cbp60g-1 snc2-1D,whereas overexpression of CBP60b leads to elevated SARD1 expression and constitutive defense responses.In addition,transient expression of CBP60b in Nicotiana benthamiana activates the expression of the pSARD1::luciferase reporter gene.Chromatin immunoprecipitation assays further showed that CBP60b is recruited to the promoter region of SARD1,suggesting that it directly regulates SARD1 expression.Interestingly,knocking out CBP60b in the wild-type background leads to ENHANCED DISEASE SUSCEPTIBILITY 1(EDS1)-dependent autoimmunity,suggesting that CBP60b is required for the expression of a guardee/decoy or a negative regulator of immunity mediated by receptors carrying an N-terminal Toll-interleukin-1 receptor-like domain.

关键词： Arabidopsis plant immunity CBP60b CBP60g SARD1 salicylic acid

Biosynthesis and Regulation of Salicylic Acid and N-Hydroxypipecolic Acid in Plant Immunity

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Molecular Plant 2020年第1期13卷 31-41页

作者： Weijie Huang Yiran Wang Xin Li Yuelin Zhang Department of Botany University of British ColumbiaVancouverBC V6T 1Z4Canada michael smith laboratories University of British ColumbiaVancouverBC V6T 1Z4Canada

Salicylic acid(SA)has long been known to be essential for basal defense and systemic acquired resistance(SAR).N-Hydroxypipecolic acid(NHP),a recently discovered plant metabolite,also plays a key role in SAR and to a lesser extent in basal resistance.Following pathogen infection,levels of both compounds are dramatically increased.Analysis of SA-or SAR-deficient mutants has uncovered how SA and NHP are biosynthesized.The completion of the SA and NHP biosynthetic pathways in Arabidopsis allowed better understanding of how they are regulated.In this review,we discuss recent progress on SA and NHP biosynthesis and their regulation in plant immunity.

关键词： plant immunity SAR SA NHP pipecolic acid

The Superior Colliculus:Cell Types,Connectivity,and Behavior

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Neuroscience Bulletin 2022年第12期38卷 1519-1540页

作者： Xue Liu Hongren Huang Terrance PSnutch Peng Cao Liping Wang Feng Wang Shenzhen Key Lab of Neuropsychiatric Modulation Guangdong Provincial Key Laboratory of Brain Connectome and BehaviorCAS Key Laboratory of Brain Connectome and Manipulationthe Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsShenzhen 518055China University of Chinese Academy of Sciences Beijing 100049China michael smith laboratories and Djavad Mowafaghian Centre for Brain Health University of British ColumbiaVancouver V6T 1Z4Canada National Institute of Biological Sciences Beijing 100049China

The superior colliculus(SC),one of the most well-characterized midbrain sensorimotor structures where visual,auditory,and somatosensory information are integrated to initiate motor commands,is highly conserved across vertebrate evolution.Moreover,cell-type-specific SC neurons integrate afferent signals within local networks to generate defined output related to innate and cognitive behaviors.This review focuses on the recent progress in understanding of phenotypic diversity amongst SC neurons and their intrinsic circuits and long-projection targets.We further describe relevant neural circuits and specific cell types in relation to behavioral outputs and cognitive functions.The systematic delineation of SC organization,cell types,and neural connections is further put into context across species as these depend upon laminar architecture.Moreover,we focus on SC neural circuitry involving saccadic eye movement,and cognitive and innate behaviors.Overall,the review provides insight into SC functioning and represents a basis for further understanding of the pathology associated with SC dysfunction.

关键词： Superior colliculus Glutamatergic neurons GABAergic neurons Neuronal circuits Innate behaviors

Negative regulation of resistance protein-mediated immunity by master transcription factors SARD_1 and CBP60g

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Journal of Integrative Plant Biology 2018年第11期60卷 1023-1027页

作者： tongjun sun wanwan liang yuelin zhang xin li department of botany university of british columbiaVancouverBC V6T 1Z4Canada michael smith laboratories university of british columbiaVancouverBC V6T 1Z4Canada

Summary Salicylic acid （SA） is an essential defence hormone in plants. Upon pathogen infection, induced biosynthesis of SA is mediated by Isochorismate synthase 1 （ICS1）, whose gene transcription is controlled mainly through two redundant transcription factors, SAR Deficient 1 （SARD0 and Calmodulin- binding protein 6o-like g （CBP60g）.

关键词： SNC Negative regulation of resistance protein-mediated immunity by master transcription factors SARD1 and CBP60g SA Figure CBP

Epigenetic regulation of N-hydroxypipecolic acid biosynthesis by the AIPP3-PHD2-CPL2 complex

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Journal of Integrative Plant Biology 2023年第12期65卷 2660-2671页

作者： Jiameng Lan Siyu Chen Joana Pico Kevin Ao Shitou Xia Shucai Wang Xin Li Simone D.Castellarin Yuelin Zhang Department of Botany University of British ColumbiaVancouverV6T 1Z4 Canada Laboratory of Plant Molecular Genetics&Crop Gene Editing School of Life SciencesLinyi UniversityLinyi276005 China Wine Research Centre Faculty of Land and Food SystemsUniversity of British ColumbiaVancouver V6T 1Z4Canada michael smith laboratories University of BritishColumbiaVancouverV6T1Z4Canada Hunan Provincial Key Laboratory of Phytohormones Hunan Agricultural UniversityChangsha 410125China College of Life Science Sichuan UniversityChengdu 610064China

N-Hydroxypipecolic acid(NHP)is a signaling molecule crucial for systemic acquired resistance(SAR),a systemic immune response in plants that provides long-lasting and broad-spectrum protection against secondary pathogen infections.To identify negative regulators of NHP biosynthesis,we performed a forward genetic screen to search for mutants with elevated expression of the NHP biosynthesis gene FLAVIN-DEPENDENT MONOOXYGENASE 1(FMO1).Analysis of two constitutive expression of FMO1(cef)and one induced expression of FMO1(ief)mutants revealed that the AIPP3–PHD2–CPL2 protein complex,which is involved in the recognition of the histone modification H3K27me3 and transcriptional repression,contributes to the negative regulation of FMO1 expression and NHP biosynthesis.Our study suggests that epigenetic regulation plays a crucial role in controlling FMO1 expression and NHP levels in plants.

关键词： plant immunity SAR epigenetic regulation NHP FMO1 H3K27me3 transcriptional repression AIPP3 PHD2 CPL2

P-Loop-Dependent NLR SNC1 Can Oligomerize and Activate Immunity in the Nucleus

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Molecular Plant 2014年第12期7卷 1801-1804页

作者： Fang Xu[a],[b],, Yu Ti Cheng[a],[b],, Paul Kapos[a], Yan Huang[a],[b] Xin Li[a],[b], [a] michael smith laboratories University of British Columbia Vancouver BC V6T 1Z4 Canada[b] Department of Botany University of British Columbia Vancouver BC V6T 1Z4 Canada

Dear Editor, Upon recognition of pathogen effectors, plant resist- ance （R） proteins trigger strong defense responses that restrict the growth and spread of pathogens. Most R pro- teins are nucleotide-binding （NB） and leucine-rich repeat （LRR） domain-containing proteins （NLRs） sharing struc- tural similarity with animal NOD-like receptors （Dodds and Rathjen, 2010）. SNC1 （Suppressor of nprl, constitutive 1） is an Arabidopsis Toll/interleukin-1 Receptor （TIR）-type NLR that was originally identified through a gain-of-function autoimmune mutant, sncl, from a forward genetic screen.

关键词： PLANT IMMUNITY ARABIDOPSIS ACCUMULATION

Recent advances in targeting the“undruggable”proteins:from drugdiscover to clinical trials

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Signal Transduction and Targeted Therapy 2023年第10期8卷 4477-4547页

作者： Xin Xie Tingting Yu Xiang Li Nan Zhang Leonard J.Foster Cheng Peng Wei Huang Gu He State Key Laboratory of Southwestern Chinese Medicine Resources College of Medical Technology and School of PharmacyChengdu University of Traditional Chinese Medicine611137 ChengduChina michael smith laboratories University of British ColumbiaVancouverBC V6T 1Z4Canada Department of Dermatology and State Key Laboratory of Biotherapy West China HospitalSichuan University610041 ChengduChina

Undruggable proteins are a class of proteins that are often characterized by large,complex structures or functions that are diffcult to interfere with using conventional drug design strategies.Targeting such undruggable targets has been considered also a great opportunity for treatment of human diseases and has attracted substantial efforts in the field of medicine.Therefore,in this review,we focus on the recent development of drug discovery targeting"undruggable"proteins and their application in clinic.To make this review well organized,we discuss the design strategies targeting the undruggable proteins,including covalent regulation,allosteric inhibition,protein-protein/DNA interaction inhibition,targeted proteins regulation,nucleic acid-based approach,immunotherapy and others.

关键词： drug diseases clinical

Calcium channels at the center of nucleotide-binding leucine-rich repeat receptor-mediated plant immunity

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Journal of Genetics and Genomics 2021年第6期48卷 429-432页

作者： Shitou Xia Xueru Liu Yuelin Zhang Hunan Provincial Key Laboratory of Phytohormones and Growth Development College of Bioscience and BiotechnologyHunan Agricultural UniversityChangsha 410128China Department of Botany University of British ColumbiaVancouverBritish Columbia V6T 1Z4Canada michael smith laboratories University of British ColumbiaVancouverBritish Columbia V6T 1Z4Canada

Higher plants utilize a variety of immune receptors to recognize pathogens and trigger defense responses.Intracellular nucleotidebinding leucine-rich repeat receptors(NLRs)are widely used for detecting pathogen effect... 详细信息

关键词： Plant immunity NLR Gslcium channel

Identification of Methylosome Components as Negative Regulators of Plant Immunity Using Chemical Genetics

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Molecular Plant 2016年第12期9卷 1620-1633页

作者： Shuai Huang Aruna Balgi Yaping Pan Meng Li Xiaoran Zhang Lilin Du Ming Zhou Michel Roberge Xin Li michael smith laboratories Department of Botany University of British Columbia Vancouver BC V6T 1Z4 Canada Department of Biochemistry and Molecular Biology University of British Columbia Vancouver BC V6T 1Z3 Canada Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine Houston TX 77030 USA National Institute of Biological Sciences Beijing 102206 China

Nucleotide-binding leucine-rich repeat （NLR） proteins serve as immune receptors in both plants and animals. To identify components required for NLR-mediated immunity, we designed and carried out a chemical genetics screen to search for small molecules that can alter immune responses in Arabidopsis thaliana. From 13 600 compounds, we identified Ro 8-4304 that was able to specifically suppress the severe autoimmune phenotypes of chs3-2D （chilling sensitive 3, 2D）, including the arrested growth morphology and heightened PR （Pathogenesis Related） gene expression. Further, six Ro 8-4304 insensitive mutants were uncovered from the Ro 8-4304-insensitive mutant （rim） screen using a mutagenized chs3-2D popula- tion. Positional cloning revealed thatriml encodes an allele of AtlCIn （I, currents; CI, chloride; n, nucleotide）. Genetic and biochemical analysis demonstrated that AtlCIn is in the same protein complex with the meth- ylosome components small nuclear ribonucleoprotein D3b （SmD3b） and protein arginine methyltransferase 5 （PRMT5）, which are required for the biogenesis of small nuclear ribonucleoproteins （snRNPs） involved in mRNA splicing. Double mutant analysis revealed that SmD3b is also involved in the sensitivity to Ro 8-4304, and the prmt5-1 chs3-2D double mutant is lethal. Loss of At/C/n, SmD3b, or PRMT5 function results in enhanced disease resistance against the virulent oomycete pathogen Hyaloperonospora arabidopsidis Noco2, suggesting that mRNA splicing plays a previously unknown negative role in plant immunity. The successful implementation of a high-throughput chemical genetic screen and the identification of a small-molecule compound affecting plant immunity indicate that chemical genetics is a powerful tool to study whole-organism plant defense pathways.

关键词： chemical genetics small molecule screening plant immunity TNL autoimmunity methylosome