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Haldar, A.

Publications and source records attributed to Haldar, A..

2 recordsLinked to original sources

Differential expansion and retention patterns of LRR-RLK genes across plant evolution

To maximize overall fitness, plants must accurately respond to a host of growth, developmental, and environmental signals throughout their life. Many of these internal and external signals are perceived by the leucine-rich repeat receptor-like kinases, which play roles in regulating growth, development, and immunity. This largest family of receptor kinases in plants can be divided into subfamilies based on conservation of the kinase domain, which demonstrates that shared evolutionary history often indicates shared molecular function. Here we investigate the evolutionary history of this family across the evolution of 112 plant species. We identify lineage-specific expansions of the malectin-domain containing subfamily LRR subfamily I primarily in the Brassicales and bryophytes. Most other plant lineages instead show a large expansion in LRR subfamily XII, which in Arabidopsis is known to contain key receptors in pathogen perception. This striking asymmetric expansion may reveal a dichotomy in the evolutionary history and adaptation strategies employed by plants. A greater understanding of the evolutionary pressures and adaptation strategies acting on members of this receptor family offers a way to improve functional predictions for orphan receptors and simplify identification of novel stress related receptors.

genomics↗

Dynamin-related Irgm proteins modulate LPS-induced caspase-4 activation and septic shock

Inflammation associated with gram-negative bacterial infections is often instigated by the bacterial cell wall component lipopolysaccharide (LPS). LPS-induced inflammation and resulting life-threatening sepsis are mediated by the two distinct LPS receptors TLR4 and caspase-4. Whereas the regulation of TLR4 activation by extracellular and phago-endosomal LPS has been studied in great detail, auxiliary host factors that specifically modulate recognition of cytosolic LPS by caspase-4 are largely unknown. This study identifies dynamin-related membrane remodeling proteins belonging to the family of Immunity related GTPases M clade (IRGM) as negative regulators of caspase-4 activation in macrophages. Phagocytes lacking expression of mouse isoform Irgm2 aberrantly activate caspase-4-dependent inflammatory responses when exposed to extracellular LPS, bacterial outer membrane vesicles or gram-negative bacteria. Consequently, Irgm2-deficient mice display increased susceptibility to caspase-4-mediated septic shock in vivo. This Irgm2 phenotype is partly reversed by the simultaneous genetic deletion of the two additional Irgm paralogs Irgm1 and Irgm3, indicating that dysregulated Irgm isoform expression disrupts intracellular LPS processing pathways that limit LPS availability for caspase-4 activation.

immunology↗