Mario Ascoli

Bio: Mario Ascoli is an academic researcher from Roy J. and Lucille A. Carver College of Medicine. The author has contributed to research in topics: Receptor & Leydig cell. The author has an hindex of 51, co-authored 150 publications receiving 7670 citations. Previous affiliations of Mario Ascoli include Population Council & Texas Tech University Health Sciences Center.

The Lutropin/Choriogonadotropin Receptor, A 2002 Perspective

Abstract: Reproduction cannot take place without the proper functioning of the lutropin/choriogonadotropin receptor (LHR). When the LHR does not work properly, ovulation does not occur in females and Leydig cells do not develop normally in the male. Also, because the LHR is essential for sustaining the elevated levels of progesterone needed to maintain pregnancy during the first trimester, disruptions in the functions of the LHR during pregnancy have catastrophic consequences. As such, a full understanding of the biology of the LHR is essential to the survival of our species. In this review we summarize our current knowledge of the structure, functions, and regulation of this important receptor.

Characterization of Several Clonal Lines of Cultured Ley dig Tumor Cells: Gonadotropin Receptors and Steroidogenic Responses*

Abstract: Several clonal lines of cultured Leydig tumor cells have been established and characterized in terms of gonadotropin receptors and steroid production. Although freshly isolated cells derived from the M5480P tumor have functional hCG receptors, only two of the five clonal lines established were shown to bind significant quantities of hCG. In these clones, steroid production can be stimulated to the same extent by hCG, cholera toxin, and 8-Br-cAMP. The other three clones bind a small amount of hCG and respond to the hormone with a marginal increase in steroidogenesis. Steroid production, however, is significantly stimulated by cholera toxin or 8-Br-cAMP. A comparison of the steroids produced by freshly isolated cells and two of the clones revealed some changes in the steroidogenic pathway. The most obvious change is an increase in the ability of the cultured cells to synthesize 20α-dihydroprogesterone (20α-hydroxypregn-4-en-3-one). These clonal lines may provide a suitable model system for the study of gona...

The Lutropin/Choriogonadotropin Receptor… 4 Years Later*

Abstract: I. Introduction IN 1989 we published a review in this journal in which we summarized, criticized, and attempted to reconcile the conflicting data that existed on the structure of the mammalian LH/CG receptor (1). Based on our analysis of the existing data we concluded that the LH/CG receptor was composed of a single polypeptide chain. Since that review was published, complementary DNAs (cDNAs) for the LH/CG receptor from several species have been cloned, sequenced, and expressed, conclusively establishing that this receptor is indeed a single polypeptide chain (2–5). The cloning of the cDNAs for the LH/CG receptor has also generated new knowledge and experimental tools that are rapidly being used to probe novel aspects of the functions and regulation of this important receptor. Since the studies leading to the cloning of the first cDNA for the LH/CG receptor have been recently summarized (6), this review will only briefly touch on this aspect and focus mainly on what has been learned since the initial clo...

The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction

Abstract: Between the 1960s and 1980s, most life scientists focused their attention on studies of nucleic acids and the translation of the coded information. Protein degradation was a neglected area, conside...

Coated pits, coated vesicles, and receptor-mediated endocytosis

Abstract: Proteins and peptides can enter cells by receptor-mediated endocytosis, a coupled process by which selected extracellular proteins or peptides are first bound to specific cell surface receptors and then rapidly internalised by the cell. Internalisation follows clustering of the receptors in specialised regions of the cell surface called coated pits that invaginate to form intracellular coated vesicles. It is now recognised that receptor-mediated endocytosis has a fundamental role in the growth, nutrition and differentiation of animal cells.

Evolving Concepts in G Protein-Coupled Receptor Endocytosis: The Role in Receptor Desensitization and Signaling

Abstract: G protein-coupled receptors (GPCRs) are seven transmembrane proteins that form the largest single family of integral membrane receptors. GPCRs transduce information provided by extracellular stimuli into intracellular second messengers via their coupling to heterotrimeric G proteins and the subsequent regulation of a diverse variety of effector systems. Agonist activation of GPCRs also initiates processes that are involved in the feedback desensitization of GPCR responsiveness, the internalization of GPCRs, and the coupling of GPCRs to heterotrimeric G protein-independent signal transduction pathways. GPCR desensitization occurs as a consequence of G protein uncoupling in response to phosphorylation by both second messenger-dependent protein kinases and G protein-coupled receptor kinases (GRKs). GRK-mediated receptor phosphorylation promotes the binding of beta-arrestins, which not only uncouple receptors from heterotrimeric G proteins but also target many GPCRs for internalization in clathrin-coated vesicles. beta-Arrestin-dependent endocytosis of GPCRs involves the direct interaction of the carboxyl-terminal tail domain of beta-arrestins with both beta-adaptin and clathrin. The focus of this review is the current and evolving understanding of the contribution of GRKs, beta-arrestins, and endocytosis to GPCR-specific patterns of desensitization and resensitization. In addition to their role as GPCR-specific endocytic adaptor proteins, beta-arrestins also serve as molecular scaffolds that foster the formation of alternative, heterotrimeric G protein-independent signal transduction complexes. Similar to what is observed for GPCR desensitization and resensitization, beta-arrestin-dependent GPCR internalization is involved in the intracellular compartmentalization of these protein complexes.

Endosome maturation: Endosome maturation

Abstract: Being deeply connected to signalling, cell dynamics, growth, regulation, and defence, endocytic processes are linked to almost all aspects of cell life and disease. In this review, we focus on endosomes in the classical endocytic pathway, and on the programme of changes that lead to the formation and maturation of late endosomes/multivesicular bodies. The maturation programme entails a dramatic transformation of these dynamic organelles disconnecting them functionally and spatially from early endosomes and preparing them for their unidirectional role as a feeder pathway to lysosomes.