Cortactin interacts with αDystrobrevin-1 and regulates murine neuromuscular junction morphology.

Neuromuscular junctions transmit signals from the nervous system to skeletal muscles, triggering their contraction, and their proper organization is essential for breathing and voluntary movements. αDystrobrevin-1 is a cytoplasmic component of the dystrophin-glycoprotein complex and has pivotal functions in regulating the integrity of muscle fibers and neuromuscular junctions. Previous studies identified that αDystrobrevin-1 functions in the organization of the neuromuscular junction and that its phosphorylation in the C-terminus is required in this process.

Expression and Roles of Lynx1, a Modulator of Cholinergic Transmission, in Skeletal Muscles and Neuromuscular Junctions in Mice.

Lynx1 is a glycosylphosphatidylinositol (GPI)-linked protein shown to affect synaptic plasticity through modulation of nicotinic acetylcholine receptor (nAChR) subtypes in the brain. Because of this function and structural similarity to α-bungarotoxin, which binds muscle-specific nAChRs with high affinity, Lynx1 is a promising candidate for modulating nAChRs in skeletal muscles. However, little is known about the expression and roles of Lynx1 in skeletal muscles and neuromuscular junctions (NMJs).

FSH mediated cAMP signalling upregulates the expression of Gα subunits in pubertal rat Sertoli cells.

Follicle Stimulating Hormone (FSH) acts via FSH-Receptor (FSH-R) by employing cAMP as the dominant secondary messenger in testicular Sertoli cells (Sc) to support spermatogenesis. Binding of FSH to FSH-R, results the recruitment of the intracellular GTP binding proteins, either stimulatory Gα or inhibitory Gα that in turn regulate cAMP production in Sc. The cytosolic concentration of cAMP being generated by FSH-R thereafter critically determines the downstream fate of the FSH signalling.

A Role for Caveolin-3 in the Pathogenesis of Muscular Dystrophies.

Caveolae are the cholesterol-rich small invaginations of the plasma membrane present in many cell types including adipocytes, endothelial cells, epithelial cells, fibroblasts, smooth muscles, skeletal muscles and cardiac muscles. They serve as specialized platforms for many signaling molecules and regulate important cellular processes like energy metabolism, lipid metabolism, mitochondria homeostasis, and mechano-transduction. Caveolae can be internalized together with associated cargo.

Pubertal down-regulation of Tetraspanin 8 in testicular Sertoli cells is crucial for male fertility.

The alarming decline in sperm count has become a global concern in the recent decades. The division and differentiation of male germ cells (Gc) into sperm are governed by Sertoli cells (Sc) upon their functional maturation during puberty. However, the roles of genes regulating pubertal maturation of Sc have not been fully determined.

Arhgef5 Binds α-Dystrobrevin 1 and Regulates Neuromuscular Junction Integrity.

The neuromuscular junctions (NMJs) connect muscle fibers with motor neurons and enable the coordinated contraction of skeletal muscles. The dystrophin-associated glycoprotein complex (DGC) is an essential component of the postsynaptic machinery of the NMJ and is important for the maintenance of NMJ structural integrity. To identify novel proteins that are important for NMJ organization, we performed a mass spectrometry-based screen for interactors of α-dystrobrevin 1 (aDB1), one of the components of the DGC.

An improved method for culturing myotubes on laminins for the robust clustering of postsynaptic machinery.

Motor neurons form specialized synapses with skeletal muscle fibers, called neuromuscular junctions (NMJs). Cultured myotubes are used as a simplified in vitro system to study the postsynaptic specialization of muscles. The stimulation of myotubes with the glycoprotein agrin or laminin-111 induces the clustering of postsynaptic machinery that contains acetylcholine receptors (AChRs).

Downregulation of Sostdc1 in Testicular Sertoli Cells is Prerequisite for Onset of Robust Spermatogenesis at Puberty.

An alarming decline in sperm count of men from several countries has become a major concern for the world community. Hormones act on testicular Sertoli cells (Sc) to regulate male fertility by governing the division and differentiation of germ cells (Gc). However, there is a limited knowledge about Sc specific gene(s) regulating the spermatogenic output of the testis.

Testosterone augments FSH signaling by upregulating the expression and activity of FSH-Receptor in Pubertal Primate Sertoli cells.

The synergistic actions of Testosterone (T) and FSH via testicular Sertoli cells (Sc) regulate male fertility. We have previously reported that the actions of these hormones (T and FSH) in infant monkey testes are restricted only to the expansion of Sc and spermatogonial cells. The robust differentiation of male Germ cells (Gc) occurs after pubertal maturation of testis.

VEGF may contribute to macrophage recruitment and M2 polarization in the decidua.

It is increasingly evident that cytokines and growth factors produced in the decidua play a pivotal role in the regulation of the local immune microenvironment and the establishment of pregnancy. One of the major growth factors produced in the decidua is vascular endothelial growth factor (VEGF), which acts not only on endothelial cells, but also on multiple other cell types, including macrophages. We sought to determine whether decidua-derived VEGF affects macrophage recruitment and polarization using human endometrial/decidual tissue samples, primary human endometrial stromal cells (ESCs), and the human monocyte cell line THP1.

Defective Wnt3 expression by testicular Sertoli cells compromise male fertility.

Testicular Sertoli cells make a niche for the division and differentiation of germ cells. Sertoli cells respond to increased follicle-stimulating hormone (FSH) and testosterone (T) levels at the onset of puberty by producing paracrine factors which affect germ cells and trigger robust onset of spermatogenesis. Such paracrine support to germ cells is absent during infancy, despite Sertoli cells being exposed to high FSH and T within the infant testis.

A Small Insulinomimetic Molecule Also Improves Insulin Sensitivity in Diabetic Mice.

Dramatic increase of diabetes over the globe is in tandem with the increase in insulin requirement. This is because destruction and dysfunction of pancreatic β-cells are of common occurrence in both Type1 diabetes and Type2 diabetes, and insulin injection becomes a compulsion. Because of several problems associated with insulin injection, orally active insulin mimetic compounds would be ideal substitute.

An integrated transcriptomics-guided genome-wide promoter analysis and next-generation proteomics approach to mine factor(s) regulating cellular differentiation.

Differential next-generation-omics approaches aid in the visualization of biological processes and pave the way for divulging important events and/or interactions leading to a functional output at cellular or systems level. To this end, we undertook an integrated Nextgen transcriptomics and proteomics approach to divulge differential gene expression of infant and pubertal rat Sertoli cells (Sc).Unlike, pubertal Sc, infant Sc are immature and fail to support spermatogenesis.

An Efficient Method for Generation of Transgenic Rats Avoiding Embryo Manipulation.

Although rats are preferred over mice as an animal model, transgenic animals are generated predominantly using mouse embryos. There are limitations in the generation of transgenic rat by embryo manipulation. Unlike mouse embryos, most of the rat embryos do not survive after male pronuclear DNA injection which reduces the efficiency of generation of transgenic rat by this method.

Sulfonoquinovosyl diacylglyceride selectively targets acute lymphoblastic leukemia cells and exerts potent anti-leukemic effects in vivo.

DNA topoisomerase II inhibitors e.g. doxorubicin and etoposide are currently used in the chemotherapy for acute lymphoblastic leukemia (ALL).

Dickkopf homolog 3 (DKK3) plays a crucial role upstream of WNT/β-CATENIN signaling for Sertoli cell mediated regulation of spermatogenesis.

Testicular Sertoli cells (Sc) are main somatic component of seminiferous tubules that govern the differentiation of germ cells (Gc) and provide them physical support. Sc are the target of follicle stimulating hormone (FSH) and testosterone (T) which are known to regulate spermatogenesis. FSH and T levels in human and sub-human male primates remain high during infancy (4-6 months post birth), similar to those during puberty.

A switch in Sertoli cell responsiveness to FSH may be responsible for robust onset of germ cell differentiation during prepubartal testicular maturation in rats.

FSH and Testosterone (T) regulate spermatogenesis via testicular Sertoli cells (Sc), which bear receptors for these hormones. Despite sufficient circulating levels of FSH and T postnatally, predominant appearance of spermatogonia B and spermatocytes is not discernible until 11 and 18 days of postnatal age, respectively, in rat testes. In an attempt to explore the underlying causes, we cultured Sc from neonatal (5- and 9-day-old) and prepubertal (12- and 19-day-old) rat testes and compared the status of FSH receptor (FSH-R) and androgen receptor (AR) signaling.