TfR2 localizes in lipid raft domains and is released in exosomes to activate signal transduction along the MAPK pathway

Calzolari, Alessia; Raggi, Carla; Deaglio, Silvia; Sposi, Nadia Maria; Stafsnes, Marit; Fecchi, Katia; Parolini, Isabella; Malavasi, Fabio; Peschle, Cesare; Sargiacomo, Massimo; Testa, Ugo

doi:10.1242/jcs.03228

Cited by 176 publications

(142 citation statements)

References 69 publications

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“…Exosomes contain peripheral membrane proteins such as MHC I and II [2] integrins, transferring receptors [62], tetraspanins [63] which are active towards downstream signaling pathways in target cells, triggering for instance calcium signaling [64], MAPK activation [65], or NKG2D signalling [66][67][68]. Exosomes also contain active lipolytic activies such as phospholipases leading to the formation of bioactive lipid mediators (fatty acids and prostaglandins) which can interact with peripheral 11 G-protein coupled receptors and nuclear receptors in target cells [9].…”

Section: Exosomes Are Signalosomesmentioning

confidence: 99%

Exosomes as intercellular signalosomes and pharmacological effectors

Record

Subra

Silvente-Poirot

et al. 2011

Biochemical Pharmacology

481

336

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International audienceCell secretion is a general process involved in various biological responses. Exosomes are part of this process and have gained considerable scientific interest in the past five years. Several steps through investigations across the last 20years can explain this interest. First characterized during reticulocyte maturation, they were next characterized as a key player in the immune response and cancer immunotherapy. More recently they were characterized as vectors of mRNAs, miRNAs and also lipid mediators able to act on target cells. They are the only type of vesicles released from an intracellular compartment from cells in viable conditions. They appear as a vectorized signaling system operating from inside a donor cell towards either the periphery, the cytosol, or possibly to the nucleus of target cells. Exosomes from normal cells trigger positive effects, whereas those from pathological ones, such as tumor cells or infected ones may trigger non-positive health effects. Therefore regulating the biogenesis and secretion of exosomes appear as a pharmacological challenge to intervene in various pathophysiologies. Exosome biogenesis and molecular content, interaction with target cells, utilisation as biomarkers, and functional effects in various pathophysiologies are considered in this review

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Section: Exosomes Are Signalosomesmentioning

confidence: 99%

Exosomes as intercellular signalosomes and pharmacological effectors

Record

Subra

Silvente-Poirot

et al. 2011

Biochemical Pharmacology

481

336

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“…These microvesicles, 30-100 nm in diameter [83], can be shed from the cell surface or via inward budding of endosome membranes [84]. Once released into extracellular space these microvesicles are termed exosomes [85] and may be involved in trans-cellular signaling [86], transfer of membrane receptors, proteins, mRNA/microRNA [87], and organelles (e.g., mitochondria) between cells. Another role may be in the delivery of infectious and toxic agents (e.g., chemotherapeutic drugs) into cells [88] (reviewed by [82]).…”

Section: Origin Of Extracellular Nucleic Acidsmentioning

confidence: 99%

Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer

Friel

Corcoran

Crown

et al. 2010

Breast Cancer Res Treat

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Early detection of cancer is vital to improved overall survival rates. At present, evidence is accumulating for the clinical value of detecting occult tumor cells in peripheral blood, plasma, and serum specimens from cancer patients. Both molecular and cellular approaches, which differ in sensitivity and specificity, have been used for such means. Circulating tumor cells and extracellular nucleic acids have been detected within blood, plasma, and sera of cancer patients. As the presence of malignant tumors are clinically determined and/or confirmed upon biopsy procurement-which in itself may have detrimental effects in terms of stimulating cancer progression/metastases-minimally invasive methods would be highly advantageous to the diagnosis and prognosis of breast cancer and the subsequent tailoring of targeted treatments for individuals, if reliable panels of biomarkers suitable for such an approach exist. Herein, we review the current advances made in the detection of such circulating tumor cells and nucleic acids, with particular emphasis on extracellular nucleic acids, specifically extracellular mRNAs and discuss their clinical relevance.

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“…TfR1 is internalized by hepatocytes via a clathrin-dependent mechanism, whereas TFR2 localizes to lipid rafts and interacts with caveolin-1. 9 Furthermore, TfR1 is recycled back to the surface, but TfR2 is delivered to multivesicular bodies and subsequently trafficked to the lysosome for degradation. 10 Additional studies are needed to elucidate the molecular machinery that regulates the different endocytic pathways used by the two TfR types.…”

Section: Hepatic Endocytosis: There Is Still a Lot To Learnmentioning

confidence: 99%

A stimulus needed for the study of membrane traffic in hepatocytes†

2009

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A major function carried out by the liver is maintenance of the blood chemistry by the continuous secretion of many different serum proteins into the blood sinusoid, transport of solutes and xenobiotics from blood to bile, and filtration of the blood through active internalization of many different receptor-ligand complexes as well as unwanted viral and bacterial pathogens. These primary hepatic secretory and endocytic functions depend on an elaborate cytoskeletal-based vesicle trafficking system that can be modified to meet the specific tasks of moving cargo outward versus inward. Despite the seminal importance of these cell biological processes to the central function of the hepatocyte and general liver physiology, their molecular mechanisms remain poorly defined and remarkably understudied by the hepatology community. Here we provide a short overview of a few important cell biological processes that are performed by hepatocytes and require our attention to better understand liver physiology and disease.

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TfR2 localizes in lipid raft domains and is released in exosomes to activate signal transduction along the MAPK pathway

Cited by 176 publications

References 69 publications

Exosomes as intercellular signalosomes and pharmacological effectors

Exosomes as intercellular signalosomes and pharmacological effectors

Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer

A stimulus needed for the study of membrane traffic in hepatocytes†

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