Optimization of brain-penetrant picolinamide derived leucine-rich repeat kinase 2 (LRRK2) inhibitors

Abstract Background Alfalfa (Medicago sativa L.) is a perennial legume extensively planted throughout the world as a high nutritive value livestock forage. Flowering time is an important agronomic trait that contributes to the production of alfalfa hay and seeds. However, the underlying molecular mechanisms of flowering time regulation in alfalfa are not well understood. Results In this study, an early-flowering alfalfa genotype 80 and a late-flowering alfalfa genotype 195 were characterized for the flowering phenotype. Our analysis revealed that the lower jasmonate (JA) content in new leaves and the downregulation of JA biosynthetic genes (i.e. lipoxygenase, the 12-oxophytodienoate reductase-like protein, and salicylic acid carboxyl methyltransferase) may play essential roles in the early-flowering phenotype of genotype 80. Further research indicated that genes encode pathogenesis-related proteins [e.g. leucine rich repeat (LRR) family proteins, receptor-like proteins, and toll-interleukin-like receptor (TIR)-nucleotide-binding site (NBS)-LRR class proteins] and members of the signaling receptor kinase family [LRR proteins, kinases domain of unknown function 26 (DUF26) and wheat leucine-rich repeat receptor-like kinase10 (LRK10)-like kinases] are related to early flowering in alfalfa. Additionally, those involved in secondary metabolism (2-oxoglutarate/Fe (II)-dependent dioxygenases and UDP-glycosyltransferase) and the proteasome degradation pathway [really interesting new gene (RING)/U-box superfamily proteins and F-box family proteins] are also related to early flowering in alfalfa. Conclusions Integrated phenotypical, physiological, and transcriptomic analyses demonstrate that hormone biosynthesis and signaling pathways, pathogenesis-related genes, signaling receptor kinase family genes, secondary metabolism genes, and proteasome degradation pathway genes are responsible for the early flowering phenotype in alfalfa. This will provide new insights into future studies of flowering time in alfalfa and inform genetic improvement strategies for optimizing this important trait.

Download Full-text

Designed leucine‐rich repeat proteins bind two muramyl dipeptide ligands

Protein Science ◽

10.1002/pro.4031 ◽

2021 ◽

Author(s):

Christina S. Kim ◽

Anne M. Brown ◽

Tijana Z. Grove ◽

Felicia A. Etzkorn

Keyword(s):

Muramyl Dipeptide ◽

Leucine Rich Repeat ◽

Repeat Proteins

Download Full-text

Nucleotide-Binding Leucine-Rich Repeat Genes CsRSF1 and CsRSF2 Are Positive Modulators in the Cucumis sativus Defense Response to Sphaerotheca fuliginea

International Journal of Molecular Sciences ◽

10.3390/ijms22083986 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3986

Author(s):

Xue Wang ◽

Qiumin Chen ◽

Jingnan Huang ◽

Xiangnan Meng ◽

Na Cui ◽

...

Keyword(s):

Cell Membrane ◽

Defense Response ◽

Nucleotide Binding ◽

Plant Defense Response ◽

Sphaerotheca Fuliginea ◽

Leucine Rich Repeat ◽

Transcript Levels ◽

Yield And Quality ◽

Leucine Rich Repeats ◽

Exogenous Substances

Cucumber powdery mildew caused by Sphaerotheca fuliginea is a leaf disease that seriously affects cucumber’s yield and quality. This study aimed to report two nucleotide-binding site-leucine-rich repeats (NBS-LRR) genes CsRSF1 and CsRSF2, which participated in regulating the resistance of cucumber to S. fuliginea. The subcellular localization showed that the CsRSF1 protein was localized in the nucleus, cytoplasm, and cell membrane, while the CsRSF2 protein was localized in the cell membrane and cytoplasm. In addition, the transcript levels of CsRSF1 and CsRSF2 were different between resistant and susceptible cultivars after treatment with exogenous substances, such as abscisic acid (ABA), methyl jasmonate (MeJA), salicylic acid (SA), ethephon (ETH), gibberellin (GA) and hydrogen peroxide (H2O2). The expression analysis showed that the transcript levels of CsRSF1 and CsRSF2 were correlated with plant defense response against S. fuliginea. Moreover, the silencing of CsRSF1 and CsRSF2 impaired host resistance to S. fuliginea, but CsRSF1 and CsRSF2 overexpression improved resistance to S. fuliginea in cucumber. These results showed that CsRSF1 and CsRSF2 genes positively contributed to the resistance of cucumber to S. fuliginea. At the same time, CsRSF1 and CsRSF2 genes could also regulate the expression of defense-related genes. The findings of this study might help enhance the resistance of cucumber to S. fuliginea.

Download Full-text

A New Comprehensive Annotation of Leucine‐Rich Repeat‐Containing Receptors in Rice

The Plant Journal ◽

10.1111/tpj.15456 ◽

2021 ◽

Author(s):

Céline Gottin ◽

Anne Dievart ◽

Marilyne Summo ◽

Gaëtan Droc ◽

Christophe Périn ◽

...

Keyword(s):

Leucine Rich Repeat

Download Full-text

The Leucine-Rich Repeat Domain Can Determine Effective Interaction Between RPS2 and Other Host Factors in Arabidopsis RPS2-Mediated Disease Resistance

Genetics ◽

10.1093/genetics/158.1.439 ◽

2001 ◽

Vol 158 (1) ◽

pp. 439-450 ◽

Cited By ~ 4

Author(s):

Diya Banerjee ◽

Xiaochun Zhang ◽

Andrew F Bent

Keyword(s):

Disease Resistance ◽

Pseudomonas Syringae ◽

Plant Disease Resistance ◽

Effective Interaction ◽

Molecular Genetic ◽

Defense Responses ◽

Host Factors ◽

Leucine Rich Repeat ◽

Domain Swap ◽

Allele Specific

Abstract Like many other plant disease resistance genes, Arabidopsis thaliana RPS2 encodes a product with nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domains. This study explored the hypothesized interaction of RPS2 with other host factors that may be required for perception of Pseudomonas syringae pathogens that express avrRpt2 and/or for the subsequent induction of plant defense responses. Crosses between Arabidopsis ecotypes Col-0 (resistant) and Po-1 (susceptible) revealed segregation of more than one gene that controls resistance to P. syringae that express avrRpt2. Many F2 and F3 progeny exhibited intermediate resistance phenotypes. In addition to RPS2, at least one additional genetic interval associated with this defense response was identified and mapped using quantitative genetic methods. Further genetic and molecular genetic complementation experiments with cloned RPS2 alleles revealed that the Po-1 allele of RPS2 can function in a Col-0 genetic background, but not in a Po-1 background. The other resistance-determining genes of Po-1 can function, however, as they successfully conferred resistance in combination with the Col-0 allele of RPS2. Domain-swap experiments revealed that in RPS2, a polymorphism at six amino acids in the LRR region is responsible for this allele-specific ability to function with other host factors.

Download Full-text