scholarly journals Nanodomains in early and later phases of FcɛRI signalling

2015 ◽  
Vol 57 ◽  
pp. 147-163 ◽  
Author(s):  
David Holowka ◽  
Barbara Baird
Keyword(s):  
Plasma Membrane ◽  
Immune Cells ◽  
Membrane Structure ◽  
Molecular Complexes ◽  
Cellular Responses ◽  
Membrane Domains ◽  
Initial Membrane ◽  
Signalling Process

Our long-term efforts to elucidate receptor-mediated signalling in immune cells, particularly transmembrane signalling initiated by FcɛRI, the receptor for IgE in mast cells, led us unavoidably to contemplate the role of the heterogeneous plasma membrane. Our early investigations with fluorescence microscopy revealed co-redistribution of certain lipids and signalling components with antigen-cross-linked IgE–FcɛRI and pointed to participation of ordered membrane domains in the signalling process. With a focus on this function, we have worked along with others to develop diverse and increasingly sophisticated tools to analyse the complexity of membrane structure that facilitates regulation and targeting of signalling events. The present chapter describes how initial membrane interactions of clustered IgE–FcɛRI lead to downstream cellular responses and how biochemical information integrated with nanoscale resolution spectroscopy and imaging is providing mechanistic insights at the level of molecular complexes.

scholarly journals RhoA- and Actin-Dependent Functions of Macrophages from the Rodent Cardiac Transplantation Model Perspective -Timing Is the Essence

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 70
Author(s):  
Malgorzata Kloc ◽  
Ahmed Uosef ◽  
Martha Villagran ◽  
Robert Zdanowski ◽  
Jacek Z. Kubiak ◽  
...  
Keyword(s):  
Immune Response ◽  
Circadian Rhythm ◽  
Immune Cells ◽  
Chronic Rejection ◽  
Cardiac Transplantation ◽  
Small Gtpase ◽  
Eukaryotic Cells ◽  
Transplantation Model

The small GTPase RhoA, and its down-stream effector ROCK kinase, and the interacting Rac1 and mTORC2 pathways, are the principal regulators of the actin cytoskeleton and actin-related functions in all eukaryotic cells, including the immune cells. As such, they also regulate the phenotypes and functions of macrophages in the immune response and beyond. Here, we review the results of our and other’s studies on the role of the actin and RhoA pathway in shaping the macrophage functions in general and macrophage immune response during the development of chronic (long term) rejection of allografts in the rodent cardiac transplantation model. We focus on the importance of timing of the macrophage functions in chronic rejection and how the circadian rhythm may affect the anti-chronic rejection therapies.

Extracellular vesicle interplay in cardiovascular pathophysiology

2021 ◽  
Author(s):  
Sherin Saheera ◽  
Vivek P Jani ◽  
Kenneth W Witwer ◽  
Shelby Kutty
Keyword(s):  
Plasma Membrane ◽  
Cardiovascular System ◽  
Lipid Bilayer ◽  
Cellular Responses ◽  
Extracellular Vesicle ◽  
Cargo Proteins ◽  
And Function ◽  
Intercellular Communications ◽  
Rna And Dna

Extracellular vesicles (EVs) are nanosized lipid bilayer-delimited particles released from cells that mediate intercellular communications and play a pivotal role in various physiological and pathological processes. Subtypes of EVs may include plasma-membrane ectosomes or microvesicles and endosomal-origin exosomes, although functional distinctions remain unclear. EVs carry cargo proteins, nucleic acids (RNA and DNA), lipids, and metabolites. By presenting or transferring this cargo to recipient cells, EVs can trigger cellular responses. Here, we summarize what is known about EV biogenesis, composition, and function, with an emphasis on the role of EVs in cardiovascular system. Additionally, we provide an update on the function of EVs in cardiovascular pathophysiology, further highlighting their potential for diagnostic and therapeutic applications.

The GTPase Rac1 selectively regulates Salmonella invasion at the apical plasma membrane of polarized epithelial cells

2001 ◽  
Vol 114 (7) ◽  
pp. 1331-1341 ◽  
Author(s):  
A.K. Criss ◽  
D.M. Ahlgren ◽  
T.S. Jou ◽  
B.A. McCormick ◽  
J.E. Casanova
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Mdck Cells ◽  
Bacterial Pathogen ◽  
Small Gtpases ◽  
Apical Plasma Membrane ◽  
Membrane Domains ◽  
Intestinal Epithelial ◽  
Actin Structure

The bacterial pathogen Salmonella typhimurium colonizes its animal hosts by inducing its internalization into intestinal epithelial cells. This process requires reorganization of the actin cytoskeleton of the apical plasma membrane into elaborate membrane ruffles that engulf the bacteria. Members of the Ρ family of small GTPases are critical regulators of actin structure, and in nonpolarized cells, the GTPase Cdc42 has been shown to modulate Salmonella entry. Because the actin architecture of epithelial cells is organized differently from that of nonpolarized cells, we examined the role of two ‘Rgr; family GTPases, Cdc42 and Rac1, in invasion of polarized monolayers of MDCK cells by S. typhimurium. Surprisingly, we found that endogenous Rac1, but not Cdc42, was activated during bacterial entry at the apical pole, and that this activation required the bacterial effector protein SopE. Furthermore, expression of dominant inhibitory Rac1 but not Cdc42 significantly inhibited apical internalization of Salmonella, indicating that Rac1 activation is integral to the bacterial entry process. In contrast, during basolateral internalization, both Cdc42 and Rac1 were activated; however, neither GTPase was required for entry. These findings, which differ significantly from previous observations in nonpolarized cells, indicate that the host cell signaling pathways activated by bacterial pathogens may vary with cell type, and in epithelial tissues may further differ between plasma membrane domains.

Systemic lupus erythematosus—management

2013 ◽  
pp. 938-947
Author(s):  
Ida Dzifa Dey ◽  
David Isenberg
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Cells ◽  
Lupus Erythematosus ◽  
Immunosuppressive Drugs ◽  
Systemic Lupus ◽  
General Management ◽  
Autoimmune Rheumatic Disease ◽  
The Future

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with varied presentation and a disease course characterized by remission and flares. Over the last 50 years the prognosis of SLE has improved considerably. The introductions of corticosteroids and later of cytotoxic drugs, dialysis, and renal transplantation were the major contributors to this improvement. Nevertheless, the treatment and general management of lupus continues to present a challenge. While lupus may, for some patients, represent a relatively mild set of problems, many others require large doses of immunosuppressive drugs, which carry long-term concerns about side effects. New immunotherapeutic drugs, with actions more closely targeted to the immune cells and molecules involved in the pathogenesis of SLE, are being introduced and the future looks promising. The role of early atherosclerosis and cardiovascular disease as a cause of death in patients with SLE is increasingly recognized and will present further challenges in the future.

scholarly journals Role of N-glycosylation in trafficking of apical membrane proteins in epithelia

2009 ◽  
Vol 296 (3) ◽  
pp. F459-F469 ◽  
Author(s):  
Olga Vagin ◽  
Jeffrey A. Kraut ◽  
George Sachs
Keyword(s):  
Plasma Membrane ◽  
Membrane Proteins ◽  
Membrane Transporters ◽  
Membrane Domains ◽  
Sorting Signals ◽  
Galectin 3 ◽  
Vectorial Functions ◽  
Apical Sorting ◽  
Golgi Network

Polarized distribution of plasma membrane transporters and receptors in epithelia is essential for vectorial functions of epithelia. This polarity is maintained by sorting of membrane proteins into apical or basolateral transport containers in the trans-Golgi network and/or endosomes followed by their delivery to the appropriate plasma membrane domains. Sorting depends on the recognition of sorting signals in proteins by specific sorting machinery. In the present review, we summarize experimental evidence for and against the hypothesis that N-glycans attached to the membrane proteins can act as apical sorting signals. Furthermore, we discuss the roles of N-glycans in the apical sorting event per se and their contribution to folding and quality control of glycoproteins in the endoplasmic reticulum or retention of glycoproteins in the plasma membrane. Finally, we review existing hypotheses on the mechanism of apical sorting and discuss the potential roles of the lectins, VIP36 and galectin-3, as putative apical sorting receptors.

Systemic lupus erythematosus—management

2013 ◽  
pp. 938-947
Author(s):  
Ida Dzifa Dey ◽  
David Isenberg
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Cells ◽  
Lupus Erythematosus ◽  
Immunosuppressive Drugs ◽  
Systemic Lupus ◽  
General Management ◽  
Autoimmune Rheumatic Disease ◽  
The Future

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with varied presentation and a disease course characterized by remission and flares. Over the last 50 years the prognosis of SLE has improved considerably. The introductions of corticosteroids and later of cytotoxic drugs, dialysis, and renal transplantation were the major contributors to this improvement. Nevertheless, the treatment and general management of lupus continues to present a challenge. While lupus may, for some patients, represent a relatively mild set of problems, many others require large doses of immunosuppressive drugs, which carry long-term concerns about side effects. New immunotherapeutic drugs, with actions more closely targeted to the immune cells and molecules involved in the pathogenesis of SLE, are being introduced and the future looks promising. The role of early atherosclerosis and cardiovascular disease as a cause of death in patients with SLE is increasingly recognized and will present further challenges in the future.

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