Role of the teneurins, teneurin C-terminal associated peptides (TCAP) in reproduction: clinical perspectives

2015 ◽  
Vol 24 (2) ◽  
Author(s):  
David A. Lovejoy ◽  
Téa Pavlović
Keyword(s):  
Cell Types ◽  
Reproductive Physiology ◽  
Corticotropin Releasing Factor ◽  
Peptide Sequence ◽  
Gene Duplications ◽  
Terminal Exon ◽  
Numerous Cell ◽  
Multicellular Organisms ◽  
G Protein Coupled

AbstractIn humans, the teneurin gene family consists of four highly conserved paralogous genes that are the result of early vertebrate gene duplications arising from a gene introduced into multicellular organisms from a bacterial ancestor. In vertebrates and humans, the teneurins have become integrated into a number of critical physiological systems including several aspects of reproductive physiology. Structurally complex, these genes possess a sequence in their terminal exon that encodes for a bioactive peptide sequence termed the ‘teneurin C-terminal associated peptide’ (TCAP). The teneurin/TCAP protein forms an intercellular adhesive unit with its receptor, latrophilin, an Adhesion family G-protein coupled receptor. It is present in numerous cell types and has been implicated in gamete migration and gonadal morphology. Moreover, TCAP is highly effective at reducing the corticotropin-releasing factor (CRF) stress response. As a result, TCAP may also play a role in regulating the stress-associated inhibition of reproduction. In addition, the teneurins and TCAP have been implicated in tumorigenesis associated with reproductive tissues. Therefore, the teneurin/TCAP system may offer clinicians a novel biomarker system upon which to diagnose some reproductive pathologies.

scholarly journals The Functional Role of Platelet-Activating Factor in Spermatozoa Physiology

2021 ◽  
Keyword(s):  
Functional Role ◽  
Platelet Activating Factor ◽  
Cell Types ◽  
Sperm Function ◽  
Male Factor Infertility ◽  
Male Factor ◽  
Synthesis Mechanism ◽  
Numerous Cell ◽  
G Protein Coupled

Platelet-activating factor (alkylacetylglycerolphosphocholine; PAF) is a potent signaling phospholipid which has been found in numerous cell types in every physiological system studied to date. In reproduction, PAF is found to have a variety of roles, for example: in ovulation, sperm function, and early preimplantation development. The goal of this mini review is to highlight PAF’s synthesis, mechanism of action and its functional role in sperm physiology. PAF functions via a G protein coupled receptor mediated pathway, which ultimately increases intracellular calcium levels to enhance sperm motility required for fertilization. Exogenous PAF was also found to increase fertilization potential of spermatozoa in cases of non-male factor infertility. Finally, the mini review explores various lifestyle factors that could potentially affect PAF levels and fertility.

Role of Transcriptional Read-Through in PRE Activity in Drosophila melanogaster

Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 79-86 ◽  
Author(s):  
P. V. Elizar’ev ◽  
D. V. Lomaev ◽  
D. A. Chetverina ◽  
P. G. Georgiev ◽  
M. M. Erokhin
Keyword(s):  
Dna Sequences ◽  
Cell Types ◽  
Transcription Terminator ◽  
Response Elements ◽  
Polycomb Response Elements ◽  
The Individual ◽  
Multicellular Organisms ◽  
Different Cell Types ◽  
Main Factor

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.

scholarly journals Evolution of the hedgehog Gene Family

Genetics ◽  
1996 ◽  
Vol 142 (3) ◽  
pp. 965-972 ◽  
Author(s):  
Sudhir Kumar ◽  
Kristi A Balczarek ◽  
Zhi-Chun Lai
Keyword(s):  
Intercellular Communication ◽  
Short Range ◽  
Gene Duplications ◽  
Future Directions ◽  
Amino Terminal ◽  
Terminal Fragment ◽  
Carboxyl Terminal ◽  
Multicellular Organisms ◽  
Amino Terminal Fragment

Abstract Effective intercellular communication is an important feature in the development of multicellular organisms. Secreted hedgehog (hh) protein is essential for both long- and short-range cellular signaling required for body pattern formation in animals. In a molecular evolutionary study, we find that the vertebrate homologs of the Drosophila hh gene arose by two gene duplications: the first gave rise to Desert hh, whereas the second produced the Indian and Sonic hh genes. Both duplications occurred before the emergence of vertebrates and probably before the evolution of chordates. The amino-terminal fragment of the hh precursor, crucial in long- and short-range intercellular communication, evolves two to four times slower than the carboxyl-terminal fragment in both Drosophila hh and its vertebrate homologues, suggesting conservation of mechanism of hh action in animals. A majority of amino acid substitutions in the amino- and carboxyl-terminal fragments are conservative, but the carboxyl-terminal domain has undergone extensive insertion-deletion events while maintaining its autocleavage protease activity. Our results point to similarity of evolutionary constraints among sites of Drosophila and vertebrate hh homologs and suggest some future directions for understanding the role of hh genes in the evolution of developmental complexity in animals.

Autoradiographic analysis and regulation of angiotensin receptor subtypes AT4, AT1, and AT(1—7) in the kidney

2001 ◽  
Vol 281 (5) ◽  
pp. F936-F947 ◽  
Author(s):  
Rajash K. Handa ◽  
Shelly E. Handa ◽  
Monica K. S. Elgemark
Keyword(s):  
Cell Types ◽  
Receptor Subtypes ◽  
Receptor Density ◽  
Angiotensin Receptor ◽  
Puromycin Aminonucleoside ◽  
Water Diuresis ◽  
Receptor System ◽  
Numerous Cell ◽  
Autoradiographic Analysis

Receptor autoradiography revealed that angiotensin AT4 receptors were abundantly expressed in normal mammalian (mouse, rat, gerbil, guinea pig, rabbit) and avian (sparrow, chicken, turkey) kidneys and were more extensively distributed than previously reported (including proximal and distal segments of the nephron, interstitium, renal artery, vein, and ureter). Angiotensin AT4 receptors were generally found to be more abundant than angiotensin AT1 receptors in mammalian kidneys, whereas angiotensin AT(1—7) receptors were not detected in either mammalian or avian kidneys. Rats subjected to various chronic treatments were found to preferentially decrease kidney AT4 receptor density (furosemide, puromycin aminonucleoside, nitro-l-arginine methyl ester), decrease kidney AT1 receptor density (bilateral ureteral obstruction), or increase kidney AT1 receptor distribution in the inner medulla (water diuresis). These results indicate that the AT4 receptor can be expressed in numerous cell types within the normal kidney of several species. Furthermore, several models of renal dysfunction and injury have been identified that selectively alter kidney AT4 density and may potentially aid in elucidating the role of this novel angiotensin receptor system in renal function.

scholarly journals Immunomodulation by Gut Microbiota: Role of Toll-Like Receptor Expressed by T Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Mariagrazia Valentini ◽  
Alessia Piermattei ◽  
Gabriele Di Sante ◽  
Giuseppe Migliara ◽  
Giovanni Delogu ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Gut Microbiota ◽  
Cell Types ◽  
Mutual Regulation ◽  
Close Relationship ◽  
Numerous Cell ◽  
Specific Receptors ◽  
And Function

A close relationship exists between gut microbiota and immune responses. An imbalance of this relationship can determine local and systemic immune diseases. In fact the immune system plays an essential role in maintaining the homeostasis with the microbiota that normally resides in the gut, while, at the same time, the gut microbiota influences the immune system, modulating number and function of effector and regulatory T cells. To achieve this aim, mutual regulation between immune system and microbiota is achieved through several mechanisms, including the engagement of toll-like receptors (TLRs), pathogen-specific receptors expressed on numerous cell types. TLRs are able to recognize ligands from commensal or pathogen microbiota to maintain the tolerance or trigger the immune response. In this review, we summarize the latest evidences about the role of TLRs expressed in adaptive T cells, to understand how the immune system promotes intestinal homeostasis, fights invasion by pathogens, and is modulated by the intestinal microbiota.

scholarly journals Endothelial Cell Inflammation and Barriers Are Regulated by the Rab26-Mediated Balance between β2-AR and TLR4 in Pulmonary Microvessel Endothelial Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Huaping Chen ◽  
Ming Yuan ◽  
Chunji Huang ◽  
Zhi Xu ◽  
Mingchun Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Membrane ◽  
Cell Surface ◽  
Cell Types ◽  
Tlr4 Expression ◽  
Barrier Dysfunction ◽  
Surface Receptors ◽  
G Protein Coupled

Rab26 GTPase modulates the trafficking of cell surface receptors, such as G protein-coupled receptors including α2-adrenergic receptors in some cell types. However, the effect of Rab26 on β2-adrenergic receptor (β2-AR) trafficking or/and Toll-like receptor 4 (TLR4) expression in human pulmonary microvascular endothelial cells (HPMECs) is still unclear. Here, we investigated the role of Rab26 in regulating the expression of β2-ARs and TLR4 in HPMECs and the effect of these receptors’ imbalance on endothelial cell barrier function. The results showed that there was unbalance expression in these receptors, where β2-AR expression was remarkably reduced, and TLR4 was increased on the cell membrane after lipopolysaccharide (LPS) treatment. Furthermore, we found that Rab26 overexpression not only upregulated β2-ARs but also downregulated TLR4 expression on the cell membrane. Subsequently, the TLR4-related inflammatory response was greatly attenuated, and the hyperpermeability of HPMECs also was partially relived. Taken together, these data suggest that basal Rab26 maintains the balance between β2-ARs and TLR4 on the cell surface, and it might be a potential therapeutic target for diseases involving endothelial barrier dysfunction.

scholarly journals Sustained Release of Prostaglandin E2in Fibroblasts Expressing Ectopically Cyclooxygenase 2 Impairs P2Y-Dependent Ca2+-Mobilization

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
María Pimentel-Santillana ◽  
Paqui G. Través ◽  
Raquel Pérez-Sen ◽  
Esmerilda G. Delicado ◽  
Paloma Martín-Sanz ◽  
...  
Keyword(s):  
Cell Types ◽  
P2y Receptors ◽  
Embryonic Fibroblasts ◽  
Extracellular Milieu ◽  
Fibroblast Migration ◽  
Cell Responses ◽  
Intracellular Calcium Mobilization ◽  
Cox 2 ◽  
G Protein Coupled

The nucleotide uridine trisphosphate (UTP) released to the extracellular milieu acts as a signaling moleculeviaactivation of specific pyrimidine receptors (P2Y). P2Y receptors are G protein-coupled receptors expressed in many cell types. These receptors mediate several cell responses and they are involved in intracellular calcium mobilization. We investigated the role of the prostanoid PGE2in P2Y signaling in mouse embryonic fibroblasts (MEFs), since these cells are involved in different ontogenic and physiopathological processes, among them is tissue repair following proinflammatory activation. Interestingly, Ca2+-mobilization induced by UTP-dependent P2Y activation was reduced by PGE2when this prostanoid was produced by MEFs transfected with COX-2 or when PGE2was added exogenously to the culture medium. This Ca2+-mobilization was important for the activation of different metabolic pathways in fibroblasts. Moreover, inhibition of COX-2 with selective coxibs prevented UTP-dependent P2Y activation in these cells. The inhibition of P2Y responses by PGE2involves the activation of PKCs and PKD, a response that can be suppressed after pharmacological inhibition of these protein kinases. In addition to this, PGE2reduces the fibroblast migration induced by P2Y-agonists such as UTP. Taken together, these data demonstrate that PGE2is involved in the regulation of P2Y signaling in these cells.

scholarly journals Extracellular Vesicles in Heart Disease: Excitement for the Future?

2014 ◽  
Vol 2 (1) ◽  
Author(s):  
Kirsty M. Danielson ◽  
Saumya Das
Keyword(s):  
Heart Disease ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Apoptotic Bodies ◽  
Cardiac Physiology ◽  
Functional Roles ◽  
Wide Range ◽  
Numerous Cell ◽  
Potential Therapeutics

Extracellular vesicles (EV), including exosomes, microvesicles and apoptotic bodies, are released from numerous cell types and are involved in intercellular communication, physiological functions and the pathology of disease. They have been shown to carry and transfer a wide range of cargo including proteins, lipids and nucleic acids. The role of EVs in cardiac physiology and heart disease is an emerging field that has produced intriguing findings in recent years. This review will outline what is currently known about EVs in the cardiovascular system, including cellular origins, functional roles and utility as biomarkers and potential therapeutics.

Abstract 200: Novel Interaction of Spinophilin with Alpha1a-Adrenergic Receptor and its Genetic Variant in Cardiovascular Cells

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Ekaterina Babaeva ◽  
Irina Gradinaru ◽  
Debra A Schwinn ◽  
Anush Oganesian
Keyword(s):  
Genetic Variant ◽  
Direct Interaction ◽  
Cell Types ◽  
Intracellular Loop ◽  
Preliminary Results ◽  
Protein Levels ◽  
Cardiovascular Cells ◽  
Novel Target ◽  
G Protein Coupled

Activation of α 1 -Adrenergic Receptors (α 1 ARs), members of the G protein-coupled receptor (GPCR) superfamily, in response to stimulation of the sympathetic nervous system by catecholamines plays a major role in regulating cardiovascular (CV) function. Among three α 1 AR subtypes (α 1a ,α 1b ,α 1d ), α 1a ARs predominate in human resistant vessels and in heart. Recently, we discovered that naturally occurring human α 1a AR-G247R (247R) genetic variant, identified in the 3 rd intracellular loop (3iL) of the receptor in highly hypertensive patient, triggers constitutive hyperproliferation in CV cells (cardiomyoblasts, smooth muscle cells (SMC) and fibroblasts), which may lead to myocardial fibrosis and remodeling. In fibroblasts and cardiomyoblasts 247R triggered hyperproliferation is due to constitutive active coupling to Gq-independent βarrestin1/MMP/EGFR/ERK dependent pathway, while in SMC it is Gq- and MMP/EGFR/ERK-dependent. Here we report that α 1a AR-WT (WT) and 247R differentially interact with ubiquitous multi-domain scaffold protein spinophilin (SPL) that binds to 3iL of several GPCRs competing with arrestin thereby prolonging their signaling. The role of SPL in CV regulation is poorly studied. We hypothesized that SPL mediates constitutive signaling of 247R and examined whether SPL directly interacts with α 1a AR-WT or 247R. Our preliminary results reveal a direct interaction of SPL with WT and 247R: the SPL-WT interaction appears to be stronger as determined by co-immunoprecipitation. Different domains of SPL differentially interact with WT or 247R. SPL 1-480aa fragment interacts stronger with WT indicating interaction with 3iL, while SPL 480-817 fragment interacts stronger with 247R. Our preliminary results also demonstrate that 247R expression in all three cell types elevates endogenous SPL protein levels. Importantly, inhibition of SPL expression with specific siRNA reduces 247R-triggered hyperproliferation in SMC and cardiomyoblasts to near normal levels, while SPL knockdown has no effect in WT cells. Thus, we identified SPL as a novel protein involved in interacting and signaling of α 1a AR and its genetic variant in CV cells and that SPL could be considered as a potentially novel target in α 1a AR-mediated cardiovascular disorders.

Vav1, but not Vav2, contributes to platelet aggregation by CRP and thrombin, but neither is required for regulation of phospholipase C

Blood ◽  
2002 ◽  
Vol 100 (10) ◽  
pp. 3561-3569 ◽  
Author(s):  
Andrew C. Pearce ◽  
Jonathan I. Wilde ◽  
Gina M. Doody ◽  
Denise Best ◽  
Osamu Inoue ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Phospholipase C ◽  
G Protein ◽  
Cell Types ◽  
Human Platelets ◽  
Glycoprotein Vi ◽  
Activation Motif ◽  
G Protein Coupled ◽  
Collagen Receptor

We have investigated the role of the Rho and Rac family small guanine triphosphate (GTP) exchange factors (RhoGEFs), Vav1 and Vav2, in the activation of platelets by the immunoreceptor tyrosine-based activation motif (ITAM)–coupled collagen receptor GPVI and by the G protein–coupled receptor agonist thrombin. The glycoprotein VI (GPVI)–specific agonist collagen-related peptide (CRP) and thrombin stimulated tyrosine phosphorylation of Vav1 but not Vav2 in human platelets. Surprisingly, however, CRP did not activate the low-molecular-weight G protein Rac and stimulated only a small increase in activity of p21-associated kinase 2 (PAK2), despite the fact that both proteins are regulated downstream of Vav1 in other cells. Further, activation of Rac and PAK2 by thrombin was maintained in platelets from mice deficient in Vav1. Activation of phospholipase C (PLC) by GPVI and thrombin was unaltered in Vav1-, Vav2-, and Vav1/Vav2-deficient platelets. A weak inhibition of late-stage aggregation to CRP and thrombin was observed in platelets deficient in Vav1 but not Vav2, whereas spreading on fibrinogen was not changed. The present results demonstrate that neither Vav1 nor Vav2 lie upstream of PLC or Rac in platelets, highlighting an important difference in their role in signaling by ITAM-coupled receptors in other cell types. The present study has provided evidence for a possible role of Vav1 but not Vav2 in the later stages of platelet aggregation.

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