A5048492882- Cell Adhesion Molecules Research
- Regulation of Appetite and Obesity
- Muscle Physiology and Disorders
- Cellular Mechanics and Interactions
- Growth Hormone and Insulin-like Growth Factors
- RNA Research and Splicing
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Biochemical Analysis and Sensing Techniques
- Renal and related cancers
- Pancreatic function and diabetes
- Axon Guidance and Neuronal Signaling
- Caveolin-1 and cellular processes
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Platelet Disorders and Treatments
- Renal Diseases and Glomerulopathies
- Nerve injury and regeneration
- Signaling Pathways in Disease
- Diet and metabolism studies
- Hippo pathway signaling and YAP/TAZ
- S100 Proteins and Annexins
- Neurobiology and Insect Physiology Research
- Neurogenesis and neuroplasticity mechanisms
- Bone and Dental Protein Studies
- Extracellular vesicles in disease
Rutgers, The State University of New Jersey
2014-2023
Johnson University
2013-2023
Merck & Co., Inc., Rahway, NJ, USA (United States)
1996-2001
Small synthetic molecules termed growth hormone secretagogues (GHSs) act on the pituitary gland and hypothalamus to stimulate amplify pulsatile (GH) release. A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of arcuate ventro-medial infundibular swine humans was cloned shown be target GHSs. On basis its pharmacological molecular characterization, this GPC-R defines a neuroendocrine pathway for control GH release supports notion that GHSs mimic an undiscovered hormone.
The recently discovered growth hormone secretagogue, ghrelin, is a potent agonist at the human secretagogue receptor 1a (hGHSR1a). To elucidate structural features of this peptide necessary for efficient binding to and activation receptor, several analogues ghrelin with various aliphatic or aromatic groups in side chain residue 3, short peptides derived from were prepared tested assay an measuring intracellular calcium elevation HEK-293 cells expressing hGHSR1a. Bulky hydrophobic 3 turned...
Motilin is a 22-amino acid peptide hormone expressed throughout the gastrointestinal (GI) tract of humans and other species. It affects gastric motility by stimulating interdigestive antrum duodenal contractions. A heterotrimeric guanosine triphosphate-binding protein (G protein)-coupled receptor for motilin was isolated from human stomach, its amino sequence found to be 52 percent identical growth secretagogues. The macrolide antibiotic erythromycin also interacted with cloned receptor,...
GH release is thought to occur under the reciprocal regulation of two hypothalamic peptides, releasing hormone (GHRH) and somatostatin, via their engagement with specific cell surface receptors on anterior pituitary somatotroph. In addition, GH-releasing such as GHRP-6 nonpeptide mimetics, L-692,429 MK-0677, stimulate through activation a distinct receptor, secretagogue receptor (GHS-R). The recent cloning GHS-R from human swine gland identifies yet third G protein-coupled (GPC-R) involved...
Galanin (GAL) is a widely distributed neuropeptide with diverse biological effects including modulation of hormone release, antinociception and modification feeding behavior. Its are mediated through G‐protein‐coupled receptors (GPCR) for which only single type has been cloned, GAL receptor 1 (GALR1). We describe the cloning second galanin type, GALR2, from rat hypothalamus. The GALR2 amino acid sequence 38% identical to GALR1 pharmacologically similar when expressed in COS‐7 cells. encoded...
Laminins contribute to basement membrane assembly through interactions of their N- and C-terminal globular domains. To further analyze this process, recombinant laminin-111 heterotrimers with deletions point mutations were generated by expression evaluated for ability self-assemble, interact nidogen-1 type IV collagen, form extracellular matrices on cultured Schwann cells immunofluorescence electron microscopy. Wild-type laminin without LG domains polymerized in contrast laminins deleted...
Understanding how the extracellular matrix impacts function of cancer stem cells (CSCs) is a significant but poorly understood problem. We report that breast CSCs produce laminin (LM) 511 promotes self-renewal and tumor initiation by engaging α6Bβ1 integrin activating Hippo transducer TAZ. Although TAZ important for CSCs, mechanism unknown. observed regulates transcription α5 subunit LM511 formation matrix. These data establish positive feedback loop involving contributes to stemness in cancer.
Netrins, a family of laminin-related molecules, have been proposed to act as guidance cues either during nervous system development or the establishment vascular system. This was clearly demonstrated for netrin-1 via its interaction with receptors DCC and UNC5s. However, mainly based on shared homologies netrin-1, netrin-4 also play role in neuronal outgrowth developmental/pathological angiogenesis interactions receptors. Here, we present high-resolution structure netrin-4, which shows...
Endoneurial laminins (Lms), β1-integrins, and dystroglycan (DG) are important for Schwann cell (SC) ensheathment myelination of axons. We now show that SC expression galactosyl-sulfatide, a Lm-binding glycolipid, precedes Lms in developing nerves. This glycolipid anchors Lm-1 -2 to surfaces by binding their LG domains enables basement membrane (BM) assembly. Revealingly, non–BM-forming fibroblasts become competent BM assembly when sulfatides intercalated into surfaces. Assembly is...
Transgenic expression of two small linker proteins restores muscle function and prolongs life span in a mouse model LAMA2 -related muscular dystrophy.
Abstract Antibodies raised against an intracellular and extracellular domain of the GH secretagogue receptor (GHS-R) confirmed that its topological orientation in lipid bilayer is as predicted for G protein-coupled receptors with seven transmembrane domains. A strategy mapping agonist-binding site human GHS-R was conceived based on our understanding ligand binding biogenic amine peptide hormone receptors. Using site-directed mutagenesis molecular modeling, we classified GHS nonpeptide...
Synthetic ligands have been identified that reset and amplify the cycle of pulsatile GH secretion by interacting with orphan GH-secretagogue receptor (GHS-R). The GHS-R is rhodopsin like, but does not obviously belong to any established G protein-coupled (GPCR) subfamilies. We recently characterized closely related family member, GPR38, as motilin receptor. A common property both receptors they sustain biological responses in continued presence their respective ligands. To efficiently...
During development, Schwann cells extend lamellipodia-like processes to segregate large- and small-caliber axons during the process of radial sorting. Radial sorting is a prerequisite for myelination arrested in human neuropathies because laminin deficiency. Experiments mice using targeted mutagenesis have confirmed that laminins 211, 411, receptors containing β1 integrin subunit are required sorting; however, which 11 α integrins can pair with forms functional receptor unknown. Here we...
During early embryogenesis, endodermal γ1-laminin expression is required for basement membrane (BM) assembly, promoting conversion of non-polar pluripotent cells into polarized epiblast. The influence laminin-111 (Lm111) and its integrin dystroglycan (DG) receptors on epiblast in embryoid bodies (EBs), a model differentiation the embryonic plate, was further investigated. Lm111 added to medium EBs initiated inner nonpolar cell epithelium with an exterior-to-central basal-to-apical...
Laminins promote early stages of peripheral nerve myelination by assembling basement membranes (BMs) on Schwann cell surfaces, leading to activation β1-integrins and other receptors. The BM composition, structural bonds ligands needed mediate this process, however, are not well understood. A mouse hypomorphic for laminin γ1-subunit expression that assembled endoneurial BMs with reduced component density exhibited an axonal sorting defect amyelination but normal proliferation, the latter...
Mutations in laminin α2-subunit (Lmα2, encoded by LAMA2) are linked to approximately 30% of congenital muscular dystrophy cases. Mice with a homozygous mutation Lama2 (dy2J mice) express nonpolymerizing form laminin-211 (Lm211) and model for ambulatory-type Lmα2-deficient dystrophy. Here, we developed transgenic dy2J mice muscle-specific expression αLNNd, laminin/nidogen chimeric protein that provides missing polymerization domain. Muscle-specific αLNNd resulted strong amelioration the...
Laminin alpha 5 (LAMA5) is a member of large family proteins that trimerise and then polymerise to form central component all basement membranes. Consequently, the protein plays an instrumental role in shaping normal development kidney, skin, neural tube, lung limb, many other organs tissues. Pathogenic mutations some laminins have been shown cause range largely syndromic conditions affecting competency membranes which they contribute. We report identification mutation polymerisation domain...
A series of structurally diverse growth hormone (GH) releasing substances have been synthesized that are distinct from the naturally occurring GH (GHRH). These synthetic molecules range family peptides and mimetics such as MK-0677. The physiological importance these their receptor is exemplified by studies in elderly. For example, when MK-0677 was administered chronically to 70- 90-year-old subjects, once daily, age-related reduced amplitude pulses reversed profile typical young adults. In...
Fast neural conduction requires accumulation of Na+ channels at nodes Ranvier. Dedicated adhesion molecules on myelinating cells and axons govern node organization. Among those, specific laminins dystroglycan complexes contribute to channel clustering peripheral by unknown mechanisms. We show that in addition facing the basal lamina, is found near nodal matrix around axons, binds components, participates initial events nodogenesis. identify dystroglycan-ligand perlecan as a novel component...