scholarly journals How the biomimetic assembly of membrane receptors into multivalent domains is regulated by a small ligand

2021 ◽  
Author(s):  
Anna Grochmal ◽  
Ben Woods ◽  
Lilia Milanesi ◽  
Manuel Perez-Soto ◽  
Salvador Tomas
Keyword(s):  
Environmental Changes ◽  
Living Cells ◽  
Membrane Receptors

In living cells, communication requires the action of membrane receptors that are activated following very small environmental changes. A binary all-or-nothing behavior follows, making the organism extremely efficient at responding...

scholarly journals Imaging of persistent cAMP signaling by internalized G protein-coupled receptors

2010 ◽  
Vol 45 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Davide Calebiro ◽  
Viacheslav O Nikolaev ◽  
Martin J Lohse
Keyword(s):  
G Protein ◽  
Intracellular Signaling ◽  
Current Model ◽  
Living Cells ◽  
G Protein Coupled Receptors ◽  
Membrane Receptors ◽  
Optical Methods ◽  
Camp Signaling ◽  
Gpcr Signaling ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) are the largest family of plasma membrane receptors. They mediate the effects of several endogenous cues and serve as important pharmacological targets. Although many biochemical events involved in GPCR signaling have been characterized in great detail, little is known about their spatiotemporal dynamics in living cells. The recent advent of optical methods based on fluorescent resonance energy transfer allows, for the first time, to directly monitor GPCR signaling in living cells. Utilizing these methods, it has been recently possible to show that the receptors for two protein/peptide hormones, the TSH and the parathyroid hormone, continue signaling to cAMP after their internalization into endosomes. This type of intracellular signaling is persistent and apparently triggers specific cellular outcomes. Here, we review these recent data and explain the optical methods used for such studies. Based on these findings, we propose a revision of the current model of the GPCR–cAMP signaling pathway to accommodate receptor signaling at endosomes.

scholarly journals Smart Polymers in Drug Delivery Applications

2019 ◽  
Vol 890 ◽  
pp. 324-339
Author(s):  
Geetha B. Heggannavar ◽  
Divya Achari ◽  
Cristiana Fernandes ◽  
Geoffrey R. Mitchell ◽  
Pedro Morouço ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Environmental Changes ◽  
Living Cells ◽  
Delivery Systems ◽  
Smart Polymers ◽  
Living Things ◽  
Polymeric Drug Delivery ◽  
Polymeric Drug ◽  
Polymeric Drug Delivery Systems

The most important components of living cells such as carbohydrates, proteins and nucleic acids are the polymeric molecules. Nature utilizes polymers both as constructive elements and as a part of the complicated cell machinery of living things. The rapid advancement in biomedical research has led to many creative applications for biocompatible polymers. With the development of newer and more potent drugs, a parallel expansion in more sophisticated drug delivery systems becomes mandatory. Smart polymeric drug-delivery systems have the ability to respond to environmental changes and consequently, alter their properties reversibly enabling an efficient and safe drug delivery. This review comprehensively discusses various aspects of these polymers classified in different categories as per the type of stimulus.

scholarly journals The Expanding Role of Vesicles Containing Aquaporins

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 179 ◽  
Author(s):  
M Martinez-Ballesta ◽  
Paula Garcia-Ibañez ◽  
Lucía Yepes-Molina ◽  
Juan Rios ◽  
Micaela Carvajal
Keyword(s):  
Environmental Changes ◽  
Cell Communication ◽  
Membrane Vesicles ◽  
Living Cells ◽  
Biotechnological Applications ◽  
Future Perspectives ◽  
Physiological Processes ◽  
Communication Processes ◽  
Other Substances

In animals and plants, membrane vesicles containing proteins have been defined as key for biological systems involving different processes such as trafficking or intercellular communication. Docking and fusion of vesicles to the plasma membrane occur in living cells in response to different stimuli, such as environmental changes or hormones, and therefore play an important role in cell homeostasis as vehicles for certain proteins or other substances. Because aquaporins enhance the water permeability of membranes, their role as proteins immersed in vesicles formed of natural membranes is a recent topic of study. They regulate numerous physiological processes and could hence serve new biotechnological purposes. Thus, in this review, we have explored the physiological implications of the trafficking of aquaporins, the mechanisms that control their transit, and the proteins that coregulate the migration. In addition, the importance of exosomes containing aquaporins in the cell-to-cell communication processes in animals and plants have been analyzed, together with their potential uses in biomedicine or biotechnology. The properties of aquaporins make them suitable for use as biomarkers of different aquaporin-related diseases when they are included in exosomes. Finally, the fact that these proteins could be immersed in biomimetic membranes opens future perspectives for new biotechnological applications.

scholarly journals Dichotomous Regulation of Lysosomes By MYC and Tfeb Controls Hematopoietic Stem Cell Fate

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 34-34
Author(s):  
Laura Garcia Prat ◽  
Kerstin B Kaufmann ◽  
Florin Schneiter ◽  
Veronique Voisin ◽  
Alex Murison ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Environmental Changes ◽  
Cell Function ◽  
Membrane Receptors ◽  
Hierarchical Organization ◽  
Lineage Commitment ◽  
Unexpected Finding ◽  
Self Renewal ◽  
Hematopoietic Stem

Human long-term hematopoietic stem cells (LT-HSC) residing at the top of the hematopoietic hierarchy must meet enormous daily demand (~10e11 cells daily) while also sustaining life-long maintenance of the stem cell pool through self-renewal. This hierarchical organization is widely thought to protect LT-HSC from exhaustion by maintaining them in a quiescent and undifferentiated state, activating only in response to microenvironment signals to generate highly proliferative but more short-lived populations including short-term HSC (ST-HSC) and committed progenitors. When called upon to exit this dormant state, HSC must respond and adapt their metabolism and nutrient uptake to meet increased bioenergetic demands for cell growth and differentiation. At the same time, the events underlying cellular and metabolic activation must also be suppressed to allow LT-HSC to re-enter quiescence and ultimately maintain the LT-HSC pool through self-renewal. Thus, proper sensing of cellular output demands must be coordinated with the cell cycle and metabolic machinery of LT-HSC to balance stem cell fates and maintain hematopoietic homeostasis. However, the regulatory circuits of this demand-adapted regulation of early hematopoiesis are largely unknown. The ability of cells to receive signals or take up nutrients depends on proteins that are embedded within the plasma membrane. These proteins move to the cell's interior through endocytosis and can be degraded in the lysosomes or rerouted back to the cell surface and reused. Moreover, lysosomes are the terminal catabolic stations of the autophagy pathway that is essential for preserving stem cell function through clearance of toxic cellular components. However, little is known about the regulation and role of lysosomes in the stem cell context. Here, we describe the unexpected finding that lysosomes, whose activity is intricately balanced by TFEB and MYC, are instrumental for regulating the stemness and differentiation properties of human LT-HSC. Furthermore, we found that TFEB, which is normally implicated in stress response, induces a constitutive lysosomal flux in unperturbed LT-HSC that actively maintains quiescence, preserves self-renewal and governs lineage commitment. These effects are accompanied by endolysosomal degradation of membrane receptors, such as the transferrin receptor 1 (TfR1), pointing to a role for TFEB in coordinating how LT-HSC sense environmental changes and initiate the earliest steps of their fate transitions and lineage commitment decisions. These transitions are regulated by a TFEB/MYC dichotomy where MYC is a driver of LT-HSC anabolism and activation and counteracts TFEB function by serving as a negative transcriptional regulator of lysosomes. Moreover, our findings further suggest that active suppression of TFEB and its downstream lysosomal degradation of TfR1 within LT-HSC is required for commitment along the erythroid lineage: activation of TFEB can abolish erythroid differentiation even after lineage commitment has occurred. In summary, we uncovered a MYC-TFEB-mediated dichotomous regulation of lysosomal activity that is required to balance anabolic and catabolic processes that ultimately impact human LT-HSC fate determination. Figure Disclosures Takayanagi: Kirin Holdings Company, Ltd: Current Employment. Dick:Bristol-Myers Squibb/Celgene: Research Funding.

Coiled-Coil Tag−Probe System for Quick Labeling of Membrane Receptors in Living Cells

2008 ◽  
Vol 3 (6) ◽  
pp. 341-345 ◽  
Author(s):  
Yoshiaki Yano ◽  
Akiko Yano ◽  
Shinya Oishi ◽  
Yukihiko Sugimoto ◽  
Gozoh Tsujimoto ◽  
...  
Keyword(s):  
Coiled Coil ◽  
Living Cells ◽  
Membrane Receptors ◽  
Probe System

Fusion and biochemical expression of membrane receptors in foreign living cells

1983 ◽  
Vol 731 (1) ◽  
pp. 121-126 ◽  
Author(s):  
Krishna Balakrishnan ◽  
J. Todd Lewis ◽  
S. Qasim Mehdi ◽  
Harden M. McConnell
Keyword(s):  
Living Cells ◽  
Membrane Receptors

Development of Fieldable Lab-on-a-Chip Systems for Detection of a Broad Array of Targets From Toxicants to Biowarfare Agents

2013 ◽  
Vol 4 (2) ◽  
Author(s):  
Jill Grimme ◽  
Travis King ◽  
Kyoo Dong Jo ◽  
Don Cropek ◽  
Aaron T. Timperman
Keyword(s):  
Synthetic Biology ◽  
Environmental Changes ◽  
Lab On A Chip ◽  
Living Cells ◽  
Cell Organelle ◽  
Trace Level ◽  
Hardware System ◽  
Recent Advances ◽  
Broad Array ◽  
Other Substances

In today's world, there is an ever growing need for lightweight, portable sensor systems to detect chemical toxicants and biological toxins. The challenges encountered with such detection systems are numerous, as there are a myriad of potential targets in various sample matrices that are often present at trace-level concentrations. At ERDC-CERL, the Lab-on-a-Chip (LoaC) group is working with a number of academic and small business collaborators to develop solutions to meet these challenges. This report will focus on recent advances in three distinct areas: (1) the development of a flexible platform to allow fieldable LoaC analyses of water samples, (2) cell-, organelle-, and synthetic biology-based toxicity sensors, and (3) nanofluidic/microfluidic interface (NMI) sample enrichment devices. To transition LoaC-based sensors from the laboratory bench to the field, a portable hardware system capable of operating a wide variety of microfluidic chip-based assays has been developed. As a demonstration of the versatility of this approach assays for the separation and quantitation of anionic contaminants (i.e., perchlorate), quantitation of heavy metals (Pb and Cd), and cell-based toxicity sensors have been developed and demonstrated. Sensors harboring living cells provide a rapid means of assessing water toxicity. Cell-based sensors exploit the sensitivity of a living cell to discrete changes in its environment to report the presence of toxicants. However, this sensitivity of cells to environmental changes also hinders their usability in nonlaboratory settings. Therefore, isolating intact organelles (i.e., mitochondria) offers a nonliving alternative that preserves the sensitivity of the living cells and allows the electrochemical reporting of the presence of a contaminant. Pursuing a synthetic biology approach has also allowed the development of nonliving reporting mechanisms that utilize engineered biological pathways for novel sensing and remediation applications. To help overcome the challenges associated with the detection of target species at trace-level concentrations, NMIs are being developed for the enrichment of charged species in solution. NMI concentrators can be classified as either electroosmotic flow or electrophoresis-dominant devices. Further advances in electrophoresis-dominant concentrators will aid in the analysis of samples that contain proteins and other substances prone to surface adsorption. These recent advances illustrate how LoaC systems provide a suitable platform for development of fieldable sensors to detect a broad range of chemical/biological pollutants and threats.

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