Biology subjects

Varshney, K.

Publications and source records attributed to Varshney, K..

4 recordsLinked to original sources

bioRxiv2026

Unequal requirement of KAI2 for AM symbiosis across angiosperms

Development of arbuscular mycorrhiza (AM), a symbiosis between plants and beneficial Glomeromycotan fungi, is largely under plant control. Several genes, required for AM development, are proposed to be regulated by the karrikin signalling module, comprising the alpha/beta hydrolase receptor KARRIKIN INSENSITIVE 2 (KAI2), the F-box protein MORE AXILLARY GROWTH2 (MAX2) and the transcriptional repressor SUPPRESSOR OF MAX2 1 (SMAX1), which is ubiquitylated for proteasomal degradation upon KAI2-ligand-induced binding to the KAI2-MAX2 complex. Rice and Brachypodium distachyon kai2 mutants are incapable of forming AM. Here, we show that in Lotus japonicus, Pisum sativum, and Nicotiana benthamiana, KAI2 only quantitatively affects AM development, indicating angiosperms vary in their requirement for KAI2-signalling to support AM. Comparative transcriptomics of L. japonicus and B. distachyon roots after treatment with fungal signalling molecules revealed some AM-relevant genes respond KAI2-independently in L. japonicus but not in B. distachyon. Consistently we obtained evidence for low-level degradation of SMAX1 in Ljkai2a,b observed through a ratiometric reporter for the SMAX1 degron (SMAX1D2). Further, we found an unexpected accumulation of SMAX1D2 in in response to AM even in wild type. Together, this suggests an unexpected role of SMAX1 accumulation in AM roots and that in AM symbiosis of L. japonicus, redundant mechanisms drive SMAX1 degradation and gene activation independently of KAI2.

plant biology↗

bioRxiv2023

C-terminal conformational changes in SCF-D3/MAX2 ubiquitin ligase are required for KAI2-mediated signaling

Karrikins (KARs) are bioactive molecules derived from burning vegetation. Plants perceive KARs through the /{beta} hydrolase KARRIKIN INSENSITIVE 2 (KAI2) that interacts with the F-box protein ubiquitin ligase MORE AXILLARY GROWTH 2 (MAX2). MAX2 also plays a role in the perception and signal activation by Strigolactone (SL), a phytohormone controlling various developmental processes in plants. SL also acts as a rhizosphere signal to activate arbuscular mycorrhiza fungi that can be exploited by parasitic plants. kai2 knockouts exhibit distinct developmental defects and therefore KAI2 is hypothesized to perceive an unidentified endogenous ligand provisionally termed KAI2-Ligand (KL). Upon KAR/KL perception, the protein complex of KAI2-MAX2 targets SUPPRESSOR OF MAX2-1/2 (SMAX1)/SMXL2 for proteasomal degradation. Despite the identification of the key components KAI2, MAX2, and SMAX1 in KAR/KL signaling, their mode of interaction and regulation remains elusive. Recently, the regulatory function of the conformational switch of MAX2 C-terminal helix (CTH) in SL signaling has been demonstrated however its role in KAR/KL signaling remained unknown. Here we address the function of MAX2-CTH dynamics both in vitro and in planta and show that the central role of CTH is conserved between SL and KAR/KL signaling pathway.

plant biology↗

bioRxiv2018

Lipid Lowering Oxopropanylindole Hydrazone Derivatives with Antioxidant and Antihyperglycemic Activity

A series of substituted oxopropanylindole hydrazone derivatives was synthesized and evaluated for anti-oxidant and anti-dyslipidemic activity. Among these 12 compounds the three compounds 6c, 7b and 7d showed good anti-oxidant activity and the compound 6c attenuataed LDL oxidation by 32%. The compounds 6c and 7d also showed good anti-dyslipidemic activity by reducing serum levels of total cholesterol (TC), phospholipids (PL) and triglycerides (TG). These two compounds were further evaluated for anti-adipogenic and anti-hyperglycemic activity, where 6c was found most active compound with 44% reduction in lipid accumulation and 20.5% and 24.3% reduction in blood glucose at 5h and 24h respectively, as compared to standard drug metformin.

biochemistry↗

bioRxiv2018

Synthesis, SAR and Docking Studies of Substituted Aryl phenylthiazolyl phenylcarboxamide as potential Protein Tyrosine Phosphatase 1B Inhibitors

Inspired by the potent PTP1B inhibitory activity reported in a novel series of substituted aryl thiazolyl phenylsulphonamides (I), sulfonyl moiety in the most active compound (I, R= OCH3, R1= CF3, 73.6% PTP1B inhibition) was replaced by benzoyl group (region B) to afford compound II which showed lesser activity (50.5% PTP1B inhibition). To optimize the activity, further structural modifications were done on compound II at region A, B and C to design and synthesize a series of 24 aryl phenylthiazolyl phenylcarboxamides for evaluation against PTP1B enzyme. Among these compounds six compounds showed good PTP1B inhibitory activity in the order of compound 38 > 30 > 29 > 37 > 22 > 19. The lowest energy conformer of compound 38 at PTP1B active site shows favorable binding similar to known PTP1B binders and explains its selectivity towards PTP1B. Compound 38 also showed promising antihyperglycemic, antidyslipidemic and insulin resistant reversal activities in vivo in STZ model and db/db mice model. Altogether, the compound 38 present an excellent candidate for future PTP1B targeted drug discovery.

pharmacology and toxicology↗