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

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.

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.

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 Neuromodulation-induced burst firing in parvalbumin interneurons of the basolateral amygdala mediates transition between fear-associated network and behavioral states

2021 ◽  
Author(s):  
Xin Fu ◽  
Eric Teboul ◽  
Jamie Maguire ◽  
Jeffrey G Tasker
Keyword(s):  
Basolateral Amygdala ◽  
Critical Role ◽  
Field Potential ◽  
Gamma Oscillations ◽  
Receptor Activation ◽  
Neuron Activity ◽  
Behavioral States ◽  
Fear Expression

Network orchestration of behavioral states involves coordinated oscillations within and between brain regions. The network communication between the basolateral amygdala (BLA) and the medial prefrontal cortex (PFC) plays a critical role in fear expression. Neuromodulatory systems play an essential role in regulating changes between behavioral states, however, a mechanistic understanding of how amygdalar circuits mediate transitions between brain and behavioral states remains largely unknown. Here, we examine the role of Gq-mediated neuromodulation of parvalbumin (PV)-expressing interneurons in the BLA in coordinating network and behavioral states using combined chemogenetics, patch clamp and field potential recordings. We demonstrate that Gq-signaling via hM3D designer receptor and α1 adrenoreceptor activation shifts the pattern of activity of the PV interneurons from tonic to phasic by stimulating a previously unknown, highly stereotyped bursting pattern of activity. This, in turn, generates bursts of inhibitory postsynaptic currents (IPSCs) and phasic firing in BLA principal neurons. The Gq-induced transition from tonic to phasic firing in BLA PV interneurons suppressed amygdalo-frontal gamma oscillations in vivo, consistent with the critical role of tonic PV neuron activity in gamma generation. The suppression of gamma oscillations by hM3D and α1 receptor activation in BLA PV interneurons also facilitated fear memory recall, in line with the inhibitory effect of gamma on fear expression. Thus, our data reveal a BLA parvalbumin neuron-specific neuromodulatory mechanism that mediates the transition to a fear-associated brain network state via regulation of amygdalo-frontal gamma oscillations.

scholarly journals D-Serine Production, Degradation, and Transport in ALS: Critical Role of Methodology

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
John P. Crow ◽  
John C. Marecki ◽  
Misty Thompson
Keyword(s):  
Amino Acid ◽  
Intracellular Transport ◽  
Critical Role ◽  
Receptor Activation ◽  
Biologically Active ◽  
Receptor Affinity ◽  
Per Se ◽  
The Brain

In mammalian systems, D-serine is perhaps the most biologically active D-amino acid described to date. D-serine is a coagonist at the NMDA-receptor, and receptor activation is dependent on D-serine binding. Because D-serine binding dramatically increases receptor affinity for glutamate, it can produce excitotoxicity without any change in glutamateper se. D-serine is twofold higher in the spinal cords of mSOD1 (G93A) ALS mice, and the deletion of serine racemase (SR), the enzyme that produces D-serine, results in an earlier onset of symptoms, but with a much slower rate of disease progression. Localization studies within the brain suggest that mSOD1 and subsequent glial activation could contribute to the alterations in SR and D-serine seen in ALS. By also degrading both D-serine and L-serine, SR appears to be a prime bidirectional regulator of free serine levelsin vivo. Therefore, accurate and reproducible measurements of D-serine are critical to understanding its regulation by SR. Several methods for measuring D-serine have been employed, and significant issues related to validation and standardization remain unresolved. Further insights into the intracellular transport and tissue-specific compartmentalization of D-serine within the CNS will aid in the understanding of the role of D-serine in the pathogenesis of ALS.

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.

Phosphoinositide 3-kinases and the regulation of platelet function

2004 ◽  
Vol 32 (2) ◽  
pp. 387-392 ◽  
Author(s):  
S.P. Jackson ◽  
C.L. Yap ◽  
K.E. Anderson
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Critical Role ◽  
Receptor Activation ◽  
Clear Understanding ◽  
Integrin Αiibβ3 ◽  
Adhesion Receptor ◽  
Input Signals

A clear understanding of the role of PI (phosphoinositide) 3-kinases in supporting the haemostatic function of platelets has been slow to evolve. In fact, insight into the roles of individual PI 3-kinase isoforms in platelet function remains rudimentary. However, based on in vitro studies using wortmannin and LY294002, there is evidence for an important role for PI 3-kinases in regulating a broad range of functional platelet responses, including primary platelet adhesion, cytoskeletal remodelling and platelet aggregation. One of the critical platelet responses involves affinity regulation of the major platelet integrin αIIbβ3, the primary receptor mediating platelet aggregation and thrombus growth. The input signals regulating integrin αIIbβ3 can be divided into three main groups: (1) Gq-coupled receptors linked to the activation of PLCβ (phospholipase Cβ); (2) Gi-coupled receptors linked to the regulation of adenylate cyclase and Rap1b; and (3) adhesion receptor signalling involving Src kinase-dependent activation of PLCγ isoforms. PI 3-kinases have not been demonstrated to play a critical role in Gq-dependent platelet activation; however, one or more PI 3-kinase isoforms appears to be important for Gi-dependent activation of Rap1b and adhesion receptor activation of PLCγ isoforms. Thus distinct co-operative PI 3-kinase signalling mechanisms appear to play an important role in regulating the adhesive function of integrin αIIbβ3.

The Role of the SLP in Autism Spectrum Disorder Screening and Assessment

2008 ◽  
Vol 15 (2) ◽  
pp. 50-59 ◽  
Author(s):  
Amy Philofsky
Keyword(s):  
Language Development ◽  
Critical Role ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Children With Asd ◽  
Prevalence Estimates ◽  
Notable Increase ◽  
Screening Assessment ◽  
Critical Components

AbstractRecent prevalence estimates for autism have been alarming as a function of the notable increase. Speech-language pathologists play a critical role in screening, assessment and intervention for children with autism. This article reviews signs that may be indicative of autism at different stages of language development, and discusses the importance of several psychometric properties—sensitivity and specificity—in utilizing screening measures for children with autism. Critical components of assessment for children with autism are reviewed. This article concludes with examples of intervention targets for children with ASD at various levels of language development.

A critical role of iNOS-derived Nitric Oxide (NO) and progesterone in implantation

1998 ◽  
Vol 5 (1) ◽  
pp. 115A-115A
Author(s):  
K CHWALISZ ◽  
E WINTERHAGER ◽  
T THIENEL ◽  
R GARFIELD
Keyword(s):  
Nitric Oxide ◽  
Critical Role
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