Sushil Kumar

Medical College of Wisconsin

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Jonathan S. Marchant

Medical College of Wisconsin

Gihan S. Gunaratne

Medical College of Wisconsin

Eugen Brailoiu

Temple University

Timothy F. Walseth

University of Minnesota

Sandip Patel

University College London

A. L. Arora

Texas Tech University

James T. Slama

University of Toledo

B. P. Kushwaha

Indian Grassland and Fodder Research Institute

V. K. Singh

Sardar Vallabhbhai Patel University of Agriculture & Technology

Yu Yuan

University College London

Cooperative Institutions

Medical College of Wisconsin

University of Minnesota

University of Cambridge

University of Toledo

Govind Ballabh Pant University of Agriculture and Technology

Central Sheep and Wool Research Institute

University College London

University of Minnesota Medical Center

Ludwig-Maximilians-Universität München

LMU Klinikum

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Progesterone receptor membrane component 1 facilitates Ca2+ signal amplification between endosomes and the endoplasmic reticulum

Journal of Biological Chemistry (2023)

Gihan S. Gunaratne Sushil Kumar Yaping Lin-Moshier James T. Slama Eugen Brailoiu

Membrane contact sites (MCSs) between endosomes and the endoplasmic reticulum (ER) are thought to act as specialized trigger zones for Ca2+ signaling, where local Ca2+ released via endolysosomal ion channels is amplified by ER Ca2+-sensitive Ca2+ channels into global Ca2+ signals. Such amplification is integral to the action of the second messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). However, functional regulators of inter-organellar Ca2+ crosstalk between endosomes and the ER remain poorly defined. Here, we identify progesterone receptor membrane component 1 (PGRMC1), an ER transmembrane protein that undergoes a unique heme-dependent dimerization, as an interactor of the endosomal two pore channel, TPC1. NAADP-dependent Ca2+ signals were potentiated by PGRMC1 overexpression through enhanced functional coupling between endosomal and ER Ca2+ stores and inhibited upon PGRMC1 knockdown. Point mutants in PGMRC1 or pharmacological manipulations that reduced its interaction with TPC1 were without effect. PGRMC1 therefore serves as a TPC1 interactor that regulates ER-endosomal coupling with functional implications for cellular Ca2+ dynamics and potentially the distribution of heme.

Component (thermodynamics)

10.1016/j.jbc.2023.105378

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Genetic variability among sheep breeds by random amplified polymorphic DNA-PCR

Kumar Shivam Atul P. Kolte B. R. Yadav Sushil Kumar Apoorva Arora

Random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) was employed to assess the genetic variability and phylogenetic relationship among six breeds of sheep, viz., Malpura, Kheri, Chokla, Garole and two crossbreds Avikalin and Bharat Merino. Twenty-four individuals from each breed/crossbred were selected randomly. Initially, 40 primers were screened, of which 16 were found polymorphic and utilized for estimation of genetic variability and phylogenetic relationship among the breeds. The genetic distance was found highest between Malpura and Garole (D=0.1428), and the lowest (D=0.0612) between Avikalin and Chokla. However, the genetic identity was observed highest (I = 0.9406) between Avikalin and Chokla and the lowest (I = 0.8669) between Malpura and Garole. The Kheri sheep was found close with Chokla (D=0.0741), followed by Malpura sheep (D=0.0902) based on genetic distance. The phylogenetic tree also showed that Avikalin and Chokla are more close, whereas Malpura and Garole are distant to each other. The present study suggested that RAPD-PCR can be used successfully for analyzing genetic variation and phylogenetic relationship among breeds of sheep.

Genetic distance

Genetic relationship

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Age and weight at first service in Chokla and their crossbred sheep

Indian Journal of Small Ruminants (The) (2001)

Sushil Kumar B. P. Kushwaha M. K. Srivastava A. L. Arora

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Convergent activation of Ca ²⁺ permeability in two-pore channel 2 through distinct molecular routes

Science Signaling (2023)

Ryo� Saito Qianru Mu Yu Yuan Marcos Rubio-Alarcón Maria Eznarriaga

TPC2 is a pathophysiologically relevant lysosomal ion channel that is activated directly by the phosphoinositide PI(3,5)P2 and indirectly by the calcium ion (Ca2+)-mobilizing molecule NAADP through accessory proteins that associate with the channel. TPC2 toggles between PI(3,5)P2-induced, sodium ion (Na+)-selective and NAADP-induced, Ca2+-permeable states in response to these cues. To address the molecular basis of polymodal gating and ion-selectivity switching, we investigated the mechanism by which NAADP and its synthetic functional agonist, TPC2-A1-N, induced Ca2+ release through TPC2 in human cells. Whereas NAADP required the NAADP-binding proteins JPT2 and LSM12 to evoke endogenous calcium ion signals, TPC2-A1-N did not. Residues in TPC2 that bind to PI(3,5)P2 were required for channel activation by NAADP but not for activation by TPC2-A1-N. The cryptic voltage-sensing region of TPC2 was required for the actions of TPC2-A1-N and PI(3,5)P2 but not for those of NAADP. These data mechanistically distinguish natural and synthetic agonist action at TPC2 despite convergent effects on Ca2+ permeability and delineate a route for pharmacologically correcting impaired NAADP-evoked Ca2+ signals.

10.1126/scisignal.adg0661

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Introgression of FecB gene in non-prolific Malpura Indian sheep for increasing litter size.

Proceedings of the 8th World Congress on Genetics Applied to Livestock Production, Belo Horizonte, Minas Gerais, Brazil, 13-18 August, 2006 (2006)

Anil Kumar Mishra A. L. Arora Sushil Kumar L. L. L. Prince V. K. Singh

Introgression

Litter

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Estimation of variance components for lamb weights and fleece yield in Avikalin sheep

The Indian Journal of Animal Sciences (2005)

Maroof Ahmad C. Singh Sushil Kumar

Data recorded on 1313 Avikalin crossbred sheep, spreading over 22 years (1980-2001) were used in present study. Traits analyzed were birth weight (BWT), weaning weight (WWT), 6-months weight (WT6), 12-months weight (WT12) and first greasy fleece yield (GFY1). Additive, phenotypic and environmental covariance between body weights increased with advancing age. The covariances between body weights at different age and first greasy fleece yield also showed similar trends. The h2 estimated under model 2, model 8 and univariate REML animal model were 0.203,0.197 and 0.265, respectively, for BWT; 0.229,0.227 and 0.138, respectively, for WWT; 0.3 12,0.390 and 0.188 for WT6,0.391,0.397 and 0.243, respectively, for WT12 and 0.373, 0.374 and 0.188, respectively, for GFYI. Model 2 and model 8 had higher h2 estimates than univariate REML procedure. The genetic, environmental and phenotypic correlations between all the traits understudy were greater than zero from moderate to high, whereas genetic correlations were slightly higher than phenotypic correlations.

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Diazirine-AIOC-NAADP, a Clickable-Photoactive NAADP Analog for Sea Urchin NAADP Binding Proteins

ACS Chemical Biology (2024)

Yuqing Zhang Zhong Zhen Guan Jennifer Gadient Sushil Kumar Gihan S. Gunaratne

Calcium ions (Ca

Diazirine

10.1021/acschembio.4c00425

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Reproductive performance of native and crossbred ewes under semi arid climate

Indian Journal of Small Ruminants (The) (2007)

B. P. Kushwaha Ravindra Kumar A. L. Arora Sushil Kumar

Data spread over 12 years, comprising reproductive and productive traits of native (Chokla and Nali) and crossbreds (Chokla synthetic, Nali synthetic and Fine wool synthetic) was used to study the effects of year, breed of ewe, age of ewe, age of ram and ewe weight at mating on oestrous cycle length (OCL), number of service /conception (NSPC), number of ewes lambing/ewe mated (ELEM), number of lambs weaned/ewe mated (LWEM), kg weaned lambs/ewe mated (KGWEM). The overall means of OCL, NSPC, ELEM, LWEM and KGWEM were 17.68 days, 1.30, 0.64, 0.58, and 7.36 kg, respectively. Breed of ewe had significant effect on all the traits. Native breeds were superior to the crossbreds in terms of ELEM, LWEM and KGWEM but inferior to OCL and NSPC. All the traits except OCL were significantly affected by year. Age of ewe had significant effect on LWEM and KGWEM. Age group of 4–5 years of ewe was observed best for all the traits studied. Age of ram had significant effect on NSPC. For lower NSPC, rams 2–4 years of age were best. Weight of ewe at mating had significant effect on NSPC and KGWEM. For lower OCL and minimum NSPC 22–24 kg and ≤21 kg ewe weight at mating, respectively, was found suitable. For maximum ELEM and LWEM, 31–33 kg body weight of ewes was found best but ≥33 kg ewe weight for maximum KGWEM. Positive correlation of all the traits, except OCL, with ewe weight at mating indicated that efforts should be made to achieve higher/optimum body weight at an early age through improved environment.

Domestic sheep reproduction

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Convergent activation of two-pore channels mediated by the NAADP-binding proteins JPT2 and LSM12

Science Signaling (2023)

Gihan S. Gunaratne Eugen Brailoiu Sushil Kumar Yu Yuan James T. Slama

The second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) evokes calcium ion (Ca 2+ ) release from endosomes and lysosomes by activating two-pore channels (TPCs) on these organelles. Rather than directly binding to TPCs, NAADP associates with proteins that indirectly confer NAADP sensitivity to the TPC complex. We investigated whether and how the NAADP-binding proteins Jupiter microtubule–associated homolog 2 (JPT2) and like-Sm protein 12 (LSM12) contributed to NAADP-TPC-Ca 2+ signaling in human cells. Biochemical and functional analyses revealed that recombinant JPT2 and LSM12 both bound to NAADP with high affinity and that endogenous JPT2 and LSM12 independently associated with TPC1 and TPC2. On the basis of knockout and rescue analyses, both NAADP-binding proteins were required to support NAADP-evoked Ca 2+ signaling and contributed to endolysosomal trafficking of pseudotyped coronavirus particles. These data reveal that the NAADP-binding proteins JPT2 and LSM12 convergently regulate NAADP-evoked Ca 2+ release and function through TPCs.

Organelle

10.1126/scisignal.adg0485

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Population Dynamics of Hyblaea puera Cram (Lepidoptera: Hyblaeidae) and Eutectona machaeralis Walk. (Lepidoptera: Pyralidae) in Teak Forest of Madhya Pradesh (India)

Indian Forester (1988)

Habib Khan R. S. Bhandari Lalji Prasad Sushil Kumar

Teak defoliator Hyblaea puera and skeletonizer Eutectoria machaeralis are serious. Insect pests of teak in IndIa which cause severe damage to green foliage durina growth period of the trees. The seasonal abundance and fluctuation in pests population associated with the incidence of attack, was studied at three location in Barela Rance, Mandla Forest Division (Madhya Pradesh, India) during 1982 to 1986. The results of five years data on population dynamics are discussed in relation to pest status of defoliator and skeletonizer. The major active period of H. puera was July and August while least active period was observed from September onwards. Generally, the pest complete 2 to 3 overlapping generatiOns during its active period. In E. machaeralis , the highest population was recorded during September. It complete 4-5 overlapping generation during its active period from August to October.

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