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Ghimire, L.

Publications and source records attributed to Ghimire, L..

2 recordsLinked to original sources

Genome-wide association study reveals candidate loci for resistance to anthracnose in blueberry

Anthracnose, caused by Colletotrichum gloeosporioides, poses a significant threat to blueberries, necessitating a deeper understanding of the genetic mechanisms underlying resistance to develop efficient breeding strategies. Here, we conducted a genome-wide association study on two distinct populations, comprising 355 advanced selections from the University of Florida Blueberry Breeding and Genomics Program. Visual scores and image analyses were used for assessing disease severity. The population was genotyped using Capture-Seq, detecting 38,379 single nucleotide polymorphisms. The study revealed a moderate narrow-sense heritability estimate ([~]0.5) for anthracnose resistance in blueberries. Minor additive loci contributing to anthracnose resistance were identified on chromosomes 2, 3, 5, 6, 8, 9, 10, 11 and 12, spanning different populations. Image analyses demonstrated heightened sensitivity, detecting more associations within both populations compared to the visual approach. Candidate gene mining flanking significant associations unveiled key defense-related proteins, such as serine/threonine protein kinases, pentatricopeptide repeat-containing proteins, E3 ubiquitin ligases that have been well-known for their roles in plant defense signaling pathways. The dissection of speculated defense-related proteins into distinct layers offers further understanding into the intricate defense responses against C. gloeosporioides. Our findings highlight the complex and quantitative resistance mechanism for anthracnose in blueberry, providing insights for breeding strategies and sustainable disease management.

genomics↗

Palmitoylation of gasdermin D directs its membrane translocation and pore formation in pyroptosis

Gasdermin D (GSDMD)-mediated macrophage pyroptosis plays a critical role in inflammation and host defense. Plasma membrane perforation elicited by caspase-cleaved GSDMD N-terminal domain (GSDMD-NT) triggers membrane rupture and subsequent pyroptotic cell death, resulting in release of pro-inflammatory IL-1{beta} and IL-18. However, the biological processes leading to its membrane translocation and pore formation are not fully understood. Here, using a proteomics approach, we identified fatty acid synthase (FASN) as a GSDMD-binding partner and demonstrated that post-translational palmitoylation of GSDMD at Cys191/Cys192 (human/mouse) led to membrane translocation of GSDMD-NT but not full-length GSDMD. GSDMD lipidation, mediated by palmitoyl acyltransferases ZDHHC5/9 and facilitated by LPS-induced reactive oxygen species (ROS), was essential for GSDMD pore-forming activity and pyroptosis. Inhibition of GSDMD palmitoylation with palmitate analog 2-bromopalmitate or a cell permeable GSDMD-specific competing peptide suppressed pyroptosis and IL-1{beta} release in macrophages, mitigated organ damage, and extended the survival of septic mice. Collectively, we establish GSDMD-NT palmitoylation as a key regulatory mechanism controlling GSDMD membrane localization and activation, providing a novel target for modulating immune activity in infectious and inflammatory diseases. One Sentence SummaryLPS-induced palmitoylation at Cys191/Cys192 is required for GSDMD membrane translocation and its pore-forming activity in macrophages.

immunology↗