scholarly journals The molecular identity of the TLQP-21 peptide receptor

2021 ◽  
Author(s):  
Bhavani S. Sahu ◽  
Megin E. Nguyen ◽  
Pedro Rodriguez ◽  
Jean Pierre Pallais ◽  
Vinayak Ghosh ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Critical Role ◽  
Receptor Activation ◽  
Signal Transduction Pathways ◽  
Endogenous Ligand ◽  
Future Studies ◽  
Peptide Receptor ◽  
Molecular Identity ◽  
Necessary And Sufficient

AbstractThe TLQP-21 neuropeptide has been implicated in functions as diverse as lipolysis, neurodegeneration and metabolism, thus suggesting an important role in several human diseases. Three binding targets have been proposed for TLQP-21: C3aR1, gC1qR and HSPA8. The aim of this review is to critically evaluate the molecular identity of the TLQP-21 receptor and the proposed multi-receptor mechanism of action. Several studies confirm a critical role for C3aR1 in TLQP-21 biological activity and a largely conserved mode of binding, receptor activation and signaling with C3a, its first-identified endogenous ligand. Conversely, data supporting a role of gC1qR and HSPA8 in TLQP-21 activity remain limited, with no signal transduction pathways being described. Overall, C3aR1 is the only receptor for which a necessary and sufficient role in TLQP-21 activity has been confirmed thus far. This conclusion calls into question the validity of a multi-receptor mechanism of action for TLQP-21 and should inform future studies.

scholarly journals The binding of NCAM to FGFR1 induces a specific cellular response mediated by receptor trafficking

2009 ◽  
Vol 187 (7) ◽  
pp. 1101-1116 ◽  
Author(s):  
Chiara Francavilla ◽  
Paola Cattaneo ◽  
Vladimir Berezin ◽  
Elisabeth Bock ◽  
Diletta Ami ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cellular Response ◽  
Critical Role ◽  
Biological Significance ◽  
Receptor Activation ◽  
Dependent Manner ◽  
Fgf Receptor ◽  
Neural Cell Adhesion ◽  
Sustained Activation

Neural cell adhesion molecule (NCAM) associates with fibroblast growth factor (FGF) receptor-1 (FGFR1). However, the biological significance of this interaction remains largely elusive. In this study, we show that NCAM induces a specific, FGFR1-mediated cellular response that is remarkably different from that elicited by FGF-2. In contrast to FGF-induced degradation of endocytic FGFR1, NCAM promotes the stabilization of the receptor, which is recycled to the cell surface in a Rab11- and Src-dependent manner. In turn, FGFR1 recycling is required for NCAM-induced sustained activation of various effectors. Furthermore, NCAM, but not FGF-2, promotes cell migration, and this response depends on FGFR1 recycling and sustained Src activation. Our results implicate NCAM as a nonconventional ligand for FGFR1 that exerts a peculiar control on the intracellular trafficking of the receptor, resulting in a specific cellular response. Besides introducing a further level of complexity in the regulation of FGFR1 function, our findings highlight the link of FGFR recycling with sustained signaling and cell migration and the critical role of these events in dictating the cellular response evoked by receptor activation.

scholarly journals PSYCHOGEOGRAPHICAL EXPERIENCE BETWEEN THE SELF AND THE PLACE

2022 ◽  
Vol 7 (1) ◽  
pp. 243-263
Author(s):  
Mohd Fadhli Shah Khaidzir ◽  
Ruzy Suliza Hashim ◽  
Noraini Md. Yusof
Keyword(s):  
Critical Role ◽  
Critical Factor ◽  
The Self ◽  
Future Research ◽  
Future Studies ◽  
Place Meaning ◽  
Solid Foundation ◽  
Self Discovery ◽  
Attachment Place

Background and Purpose: The absence of psychogeographical awareness is a critical factor contributing to the lackadaisical attitudes towards the place and its environment. As a result, it enables an individual to fully experience a location, both physically and intellectually, while also gaining a feeling of self-discovery and self-realisation.   Methodology: The purpose of this study was to examine the responses of a group of individuals who participated in a field observation. 40 participants from a Malaysian university's foundation level were brought to Malacca to experience the environment's geographical scenery at their own leisure. The survey data was then manually transcribed and analysed in accordance with the study's aim.   Findings: Interactions with individuals and observation of features in the countryside and urban surroundings enabled participants to go on a psychogeographical journey that influenced their way of thinking and behaving. All participants felt that the journey had influenced their experiences and perspectives on their thinking and behaviour, highlighting the critical role of this notion in establishing the connection between place and self.   Contributions:  The findings of this study provide a solid foundation for future research in the field of psychogeography. The data may be used as a baseline for future studies to determine whether a comparable impact exists in other locations, with or without significant features like those found in Malacca.   Keywords: Psychogeography, place attachment, place meaning, self-discovery, Malacca.   Cite as: Khaidzir, M. F. S., Hashim, R. S., & Md. Yusof, N. (2022). Psychogeographical experience between the self and the place.  Journal of Nusantara Studies, 7(1), 243-263. http://dx.doi.org/10.24200/jonus.vol7iss1pp243-263

The Critical Role of Transmembrane Prolines in Human Prostacyclin Receptor Activation

2002 ◽  
Vol 61 (5) ◽  
pp. 1202-1210 ◽  
Author(s):  
Jeremiah Stitham ◽  
Kathleen A. Martin ◽  
John Hwa
Keyword(s):  
Critical Role ◽  
Receptor Activation ◽  
Prostacyclin Receptor

The Ig-like domain of human GM-CSF receptor α plays a critical role in cytokine binding and receptor activation

2010 ◽  
Vol 426 (3) ◽  
pp. 307-317 ◽  
Author(s):  
Shamaruh Mirza ◽  
Andrew Walker ◽  
Jinglong Chen ◽  
James M. Murphy ◽  
Ian G. Young
Keyword(s):  
Structural Alignment ◽  
Critical Role ◽  
Receptor Activation ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Subsequent Activation ◽  
Macrophage Colony ◽  
Key Residues ◽  
Stimulating Factor

GM-CSF (granulocyte/macrophage colony-stimulating factor) is an important mediator of inducible haemopoiesis and inflammation, and has a critical role in the function of alveolar macrophages. Its clinical applications include the mobilization of haemopoietic progenitors, and a role as an immune stimulant and vaccine adjuvant in cancer patients. GM-CSF signals via a specific α receptor (GM-CSFRα) and the shared hβc (human common β-subunit). The present study has investigated the role of the Ig-like domain of GM-CSFRα in GM-CSF binding and signalling. Deletion of the Ig-like domain abolished direct GM-CSF binding and decreased growth signalling in the presence of hβc. To locate the specific residues in the Ig-like domain of GM-CSFRα involved in GM-CSF binding, a structural alignment was made with a related receptor, IL-13Rα1 (interleukin-13 receptor α1), whose structure and mode of interaction with its ligand has recently been elucidated. Mutagenesis of candidate residues in the predicted region of interaction identified Val51 and Cys60 as having critical roles in binding to the α receptor, with Arg54 and Leu55 also being important. High-affinity binding in the presence of hβc was strongly affected by mutation of Cys60 and was also reduced by mutation of Val51, Arg54 and Leu55. Of the four key residues, growth signalling was most severely affected by mutation of Cys60. The results indicate a previously unrecognized role for the Ig-like domain, and in particular Cys60, of GM-CSFRα in the binding of GM-CSF and subsequent activation of cellular signalling.

Molecular mechanisms of GABAB receptor activation: new insights from the mechanism of action of CGP7930, a positive allosteric modulator

2004 ◽  
Vol 32 (5) ◽  
pp. 871-872 ◽  
Author(s):  
V. Binet ◽  
C. Goudet ◽  
C. Brajon ◽  
L. Le Corre ◽  
F. Acher ◽  
...  
Keyword(s):  
G Protein ◽  
Mechanism Of Action ◽  
Molecular Mechanisms ◽  
Gabab Receptor ◽  
Receptor Activation ◽  
G Protein Coupled Receptors ◽  
Class Iii ◽  
G Protein Coupled ◽  
New Strategies

The GABAB (γ-aminobutyric acid-B) receptor is composed of two subunits, GABAB1 and GABAB2. Both subunits share structural homology with other class-III G-protein-coupled receptors. They contain two main domains, a heptahelical domain typical of all G-protein-coupled receptors and a large ECD (extracellular domain). It has not been demonstrated whether the association of these two subunits is always required for function. However, GABAB2 plays a major role in coupling with G-proteins, and GABAB1 has been shown to bind GABA. To date, only ligands interacting with GABAB1-ECD have been identified. In the present study, we explored the mechanism of action of CGP7930, a compound described as a positive allosteric regulator of the GABAB receptor. We have shown that it can weakly activate the wild-type GABAB receptor, but also the GABAB2 expressed alone, thus being the first described agonist of GABAB2. CGP7930 retains its weak agonist activity on a GABAB2 subunit deleted of its ECD. Thus the heptahelical domain of GABAB2 behaves similar to a rhodopsin-like receptor. These results open new strategies for studying the mechanism of activation of GABAB receptor and examine any possible role of GABAB2.

scholarly journals Critical Role of a Conserved Intramembrane Tyrosine Residue in Angiotensin II Receptor Activation

1995 ◽  
Vol 270 (17) ◽  
pp. 9702-9705 ◽  
Author(s):  
László Hunyady ◽  
Márta Bor ◽  
Tamás Balla ◽  
Kevin J. Catt
Keyword(s):  
Angiotensin Ii ◽  
Critical Role ◽  
Receptor Activation ◽  
Tyrosine Residue ◽  
Angiotensin Ii Receptor

scholarly journals Essential role of spi-1–like (spi-1l) in zebrafish myeloid cell differentiation

Blood ◽  
2009 ◽  
Vol 113 (9) ◽  
pp. 2038-2046 ◽  
Author(s):  
Alex Bukrinsky ◽  
Kevin J. P. Griffin ◽  
Yan Zhao ◽  
Shuo Lin ◽  
Utpal Banerjee
Keyword(s):  
Functional Analysis ◽  
Transcription Factor ◽  
Cell Differentiation ◽  
Essential Role ◽  
Critical Role ◽  
Myeloid Cell ◽  
Myeloid Differentiation ◽  
Adult Kidney ◽  
Necessary And Sufficient

The ETS protein Spi-1/Pu.1 plays a pivotal and widespread role throughout hematopoiesis in many species. This study describes the identification, characterization, and functional analysis of a new zebrafish spi transcription factor spi-1–like (spi-1l) that is expressed in primitive myeloid cells, erythro-myelo progenitor cells, and in the adult kidney. Spi-1l functions genetically downstream of etsrp, scl, and spi-1/pu.1 in myeloid differentiation. Spi-1l is coexpressed in a subset of spi-1/pu.1 cells and its function is necessary and sufficient for macrophage and granulocyte differentiation. These results establish a critical role for spi-1l in zebrafish myeloid cell differentiation.

scholarly journals Psychedelics and virtual reality: parallels and applications

2020 ◽  
Vol 10 ◽  
pp. 204512532094835
Author(s):  
Jacob S. Aday ◽  
Christopher C. Davoli ◽  
Emily K. Bloesch
Keyword(s):  
Virtual Reality ◽  
Conscious Experience ◽  
Critical Role ◽  
Scientific Interest ◽  
Future Studies ◽  
Therapeutic Uses ◽  
Mental Experience ◽  
Psychedelic Drugs ◽  
Traditional Therapies

Psychedelic drugs and virtual reality (VR) each have the capacity to disrupt the rigidity and limitations of typical conscious experience. This article delineates the parallels among psychedelic and VR states as well as their potential synergistic applications in clinical and recreational settings. Findings indicate that, individually, psychedelics and VR are used in analogous ways to alter sensory experience and evoke awe. They are also both used in tandem with traditional therapies to treat a variety of mood disorders; their shared capacity to transiently alter perspective and disrupt rigid patterns of mental experience may underly their analogous and transdiagnostic therapeutic uses. In terms of their combined applications, a number of recreational users currently utilize psychedelics and VR together to enhance their experience. We propose that VR may be a useful tool for preparing hallucinogen-naïve participants in clinical trials for the sensory distortions experienced in psychedelic states. Given the critical role of “setting” in psychedelic treatment outcomes, we also detail how VR could be used to optimize the environment in psychedelic sessions. Finally, we provide considerations for future studies and detail how advancements in psychedelic and VR research can inform one another. Collectively, this article outlines a number of connections between psychedelics and VR, and, more broadly, is representative of growing scientific interest into the interactions among technology, psychopharmacology, and mental health.

scholarly journals Recent advances in understanding the role of leptin in energy homeostasis

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 451
Author(s):  
Heike Münzberg ◽  
Prachi Singh ◽  
Steven B. Heymsfield ◽  
Sangho Yu ◽  
Christopher D. Morrison
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Energy Homeostasis ◽  
Critical Role ◽  
Early Data ◽  
Dynamic Changes ◽  
Leptin Signaling ◽  
Future Studies ◽  
Physiological Adaptations

The hormone leptin plays a critical role in energy homeostasis, although our overall understanding of acutely changing leptin levels still needs improvement. Several developments allow a fresh look at recent and early data on leptin action. This review highlights select recent publications that are relevant for understanding the role played by dynamic changes in circulating leptin levels. We further discuss the relevance for our current understanding of leptin signaling in central neuronal feeding and energy expenditure circuits and highlight cohesive and discrepant findings that need to be addressed in future studies to understand how leptin couples with physiological adaptations of food intake and energy expenditure.

scholarly journals Bacteriocins from Lactic Acid Bacteria. A Powerful Alternative as Antimicrobials, Probiotics, and Immunomodulators in Veterinary Medicine

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 979
Author(s):  
Juan Carlos Hernández-González ◽  
Abigail Martínez-Tapia ◽  
Gebim Lazcano-Hernández ◽  
Blanca Estela García-Pérez ◽  
Nayeli Shantal Castrejón-Jiménez
Keyword(s):  
Veterinary Medicine ◽  
Lactic Acid ◽  
Antimicrobial Resistance ◽  
Lactic Acid Bacteria ◽  
Mechanism Of Action ◽  
Bacterial Resistance ◽  
Animal Health ◽  
Critical Role ◽  
Bacteria And Fungi

In the search for an alternative treatment to reduce antimicrobial resistance, bacteriocins shine a light on reducing this problem in public and animal health. Bacteriocins are peptides synthesized by bacteria that can inhibit the growth of other bacteria and fungi, parasites, and viruses. Lactic acid bacteria (LAB) are a group of bacteria that produce bacteriocins; their mechanism of action can replace antibiotics and prevent bacterial resistance. In veterinary medicine, LAB and bacteriocins have been used as antimicrobials and probiotics. However, another critical role of bacteriocins is their immunomodulatory effect. This review shows the advances in applying bacteriocins in animal production and veterinary medicine, highlighting their biological roles.

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