Clathrin-mediated endocytosis of FITC-albumin in alveolar type II epithelial cell line RLE-6TN

Yumoto, Ryoko; Nishikawa, Hiromi; Okamoto, Miho; Katayama, Hirokazu; Nagai, Junya; Takano, Mikihisa

doi:10.1152/ajplung.00173.2005

Cited by 91 publications

(97 citation statements)

References 43 publications

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“…The concentrations of both inhibitors employed were effective at inhibiting the uptake of FITC-albumin in type II and type I-like cells as well as in RLE-6TN cells. 10,14) In addition, potassium depletion exhibited only a slight decrease in FITC-insulin uptake in both cells (Fig. 3C).…”

Section: Discussionmentioning

confidence: 88%

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Mechanism of Insulin Uptake in Rat Alveolar Type II and Type I-Like Epithelial Cells

Ikehata

Yumoto

Kato

et al. 2009

Biological & Pharmaceutical Bulletin

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The alveolar epithelium is comprised of type II and type I cells, which are two morphologically and functionally different epithelial cells. Alveolar type I cells, which are squamous and cover more than 90% of the alveolar surface area, play a major role in gas exchange. 1,2) On the other hand, alveolar type II cells are cuboidal and outnumber type I cells, although type II cells occupy less than 10% of the surface area even when their apical microvilli are taken into consideration.1,2) In addition, type II cells have multiple functions such as surfactant production and secretion, and serve as type I cell progenitors.2)The majority of protein and peptide therapeutic drugs were developed as injection formulations, and have a variety of problems, especially for patients, in terms of safety, pain, and needle phobia. 3,4) Recently, the lung has attracted a great deal of interest as an alternative administration route for protein and peptide drugs. 3,5) The inhalation pulmonary delivery system, which may enable the systemic absorption of protein and peptide drugs, has been extensively studied.6) In particular, clinical research on inhaled insulin has confirmed the efficacy and safety of inhaled insulin in the treatment of diabetes mellitus. 7) In addition, the bioavailability of inhaled insulin via the lung is greater compared to other non-invasive routes such as the gut and nose. 8)Previous studies concerning protein transport across alveolar epithelia have suggested that the transport system most likely to be involved is endocytosis. 9) We also have studied the transport of albumin in alveolar epithelial cells, and found that albumin is internalized into type II and type I cells via a clathrin-mediated endocytic pathway with greater uptake activity in type II cells than in type I cells.10) These findings indicate that despite the much smaller surface area of type II cells compared to type I cells, type II cells most likely play an important role in the endocytic transport of proteins in alveolar epithelia.In the case of small proteins (peptides) such as insulin, both paracellular and transcellular routes may be involved in alveolar epithelial transport.1) Bur et al. 11) reported that in human primary cultured alveolar type I-like epithelial cells, the apparent permeability coefficient of insulin was comparable to that reported for dextran, indicating that a specific, transcellular transport process is not involved. On the other hand, the alveolar epithelial junction was reported to be tighter than other epithelia, 1) suggesting that the contribution of a paracellular route for insulin in alveolar epithelial transport may not be so high. Furthermore, it has been reported that megalin serves as an endocytic receptor for insulin uptake in rat renal proximal tubule cells, 12) and that megalin is also expressed in alveolar epithelial cells.13) Thus, it is possible that an endocytic pathway is involved in insulin transport in alveolar epithelia. However, little information is available concerning the handling of insu...

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Section: Discussionmentioning

confidence: 88%

“…We previously characterized FITC-albumin uptake in rat primary cultured alveolar type II and type I-like epithelial cells as well as in RLE-6TN cells, an established cell line having some characteristics of type II cells. 10,14,15) In this study, the characteristics of FITC-insulin uptake were further examined.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Insulin Uptake in Rat Alveolar Type II and Type I-Like Epithelial Cells

Ikehata

Yumoto

Kato

et al. 2009

Biological & Pharmaceutical Bulletin

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“…PAO is a widely used inhibitor of clathrin-mediated endocytosis (28,29) that completely blocks the endocytosis of GABA B Rs (Fig. S2).…”

Section: Resultsmentioning

confidence: 99%

Prolonged activation of NMDA receptors promotes dephosphorylation and alters postendocytic sorting of GABA _B receptors

Terunuma

Vargas

Wilkins

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

109

117

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Slow and persistent synaptic inhibition is mediated by metabotropic GABA B receptors (GABA B Rs). GABA B Rs are responsible for the modulation of neurotransmitter release from presynaptic terminals and for hyperpolarization at postsynaptic sites. Postsynaptic GABA B Rs are predominantly found on dendritic spines, adjacent to excitatory synapses, but the control of their plasma membrane availability is still controversial. Here, we explore the role of glutamate receptor activation in regulating the function and surface availability of GABA B Rs in central neurons. We demonstrate that prolonged activation of NMDA receptors (NMDA-Rs) leads to endocytosis, a diversion from a recycling route, and subsequent lysosomal degradation of GABA B Rs. These sorting events are paralleled by a reduction in GABA B R-dependent activation of inwardly rectifying K + channel currents. Postendocytic sorting is critically dependent on phosphorylation of serine 783 (S783) within the GABA B R2 subunit, an established substrate of AMP-dependent protein kinase (AMPK). NMDA-R activation leads to a rapid increase in phosphorylation of S783, followed by a slower dephosphorylation, which results from the activity of AMPK and protein phosphatase 2A, respectively. Agonist activation of GABA B Rs counters the effects of NMDA. Thus, NMDA-R activation alters the phosphorylation state of S783 and acts as a molecular switch to decrease the abundance of GABA B Rs at the neuronal plasma membrane. Such a mechanism may be of significance during synaptic plasticity or pathological conditions, such as ischemia or epilepsy, which lead to prolonged activation of glutamate receptors.he availability of neurotransmitter receptors, a major determinant of synaptic efficacy, is regulated by coordinated mechanisms of intracellular trafficking that deliver newly synthesized receptors to the plasma membrane and remove them for storage, recycling, or degradation (1). The molecular mechanisms controlling the availability of GABA B receptors (GABA B Rs), which are central players in the modulation of excitatory and inhibitory synaptic activity, are unclear.GABA B Rs mediate slow and prolonged inhibitory synaptic signals (2, 3). Consistent with these roles, modifications in the function of GABA B Rs are implicated in epilepsy, anxiety, stress, sleep disorders, nociception, depression, cognition, and addictive mechanisms to drugs of abuse (3-7). GABA B Rs are members of the G protein-coupled receptor (GPCR) superfamily and are obligatory heteromers composed of two related subunits, namely GABA B R1 and GABA B R2 (3, 8). GABA B R1 binds agonist with high affinity, whereas GABA B R2 mediates coupling to Gαi (9, 10). GABA B Rs are located in GABA-ergic and glutamatergic pre-and postsynaptic terminals, but their distribution does not coincide with the active zone, postsynaptic density, or inhibitory postsynaptic specializations. Rather, they are perisynaptic receptors activated by GABA spillover (3, 11). Stimulation of GABA B Rs decreases the levels of cAMP, inhibits neurotr...

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“…It has now been demonstrated that, similarly to that of in the kidney proximal tubule, excess intra-alveolar albumin can be taken up by the alveolar epithelial cells by a clathrin-mediated endocytic process after albumin bound to the multiligand receptor megalin (21,265,266). The system appears to have the necessary capacity to remove large amounts of alveolar albumin (21), highlighting its potential relevance in alveolar epithelial fluid balance in ALI.…”

Section: L669 Acute Lung Injury and Barrier Dysfunctionmentioning

confidence: 99%

Novel concepts of acute lung injury and alveolar-capillary barrier dysfunction

Herold

Gabrielli

Vadász

2013

American Journal of Physiology-Lung Cellular and Molecular Phys

178

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Herold S, Gabrielli NM, Vadász I. Novel concepts of acute lung injury and alveolar-capillary barrier dysfunction. Am J Physiol Lung Cell Mol Physiol 305: L665-L681, 2013. First published September 13, 2013 doi:10.1152/ajplung.00232.2013In this review we summarize recent major advances in our understanding on the molecular mechanisms, mediators, and biomarkers of acute lung injury (ALI) and alveolar-capillary barrier dysfunction, highlighting the role of immune cells, inflammatory and noninflammatory signaling events, mechanical noxae, and the affected cellular and molecular entities and functions. Furthermore, we address novel aspects of resolution and repair of ALI, as well as putative candidates for treatment of ALI, including pharmacological and cellular therapeutic means. alveolar-capillary barrier dysfunction; molecular mechanism; pharmacological and cell-based therapy; pulmonary edema; zaacute lung injury/acute respiratory distress syndrome Immune Cells and Inflammatory Signaling Pathways in ALIOne of the central concepts in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is that an unbalanced quantity or quality of the inflammatory response aggravates epithelial or endothelial injury. This includes a dysregulated recruitment of leukocytes and/or an exaggerated activation of these cells; inappropriate expression of cytokines, lipid mediators, or reactive oxygen species; enhanced activation of death receptor signaling (97,98,140,207,240); or an uncontrolled activity of platelets or the coagulation cascade (154). In general, these responses are initiated and maintained by recognition of danger-or pathogen-associated molecular patterns

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Clathrin-mediated endocytosis of FITC-albumin in alveolar type II epithelial cell line RLE-6TN

Cited by 91 publications

References 43 publications

Mechanism of Insulin Uptake in Rat Alveolar Type II and Type I-Like Epithelial Cells

Mechanism of Insulin Uptake in Rat Alveolar Type II and Type I-Like Epithelial Cells

Prolonged activation of NMDA receptors promotes dephosphorylation and alters postendocytic sorting of GABA _B receptors

Novel concepts of acute lung injury and alveolar-capillary barrier dysfunction

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Clathrin-mediated endocytosis of FITC-albumin in alveolar type II epithelial cell line RLE-6TN

Cited by 91 publications

References 43 publications

Mechanism of Insulin Uptake in Rat Alveolar Type II and Type I-Like Epithelial Cells

Mechanism of Insulin Uptake in Rat Alveolar Type II and Type I-Like Epithelial Cells

Prolonged activation of NMDA receptors promotes dephosphorylation and alters postendocytic sorting of GABA B receptors

Novel concepts of acute lung injury and alveolar-capillary barrier dysfunction

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Prolonged activation of NMDA receptors promotes dephosphorylation and alters postendocytic sorting of GABA _B receptors