Inhibition of Na+âH+ exchange impairs receptor-mediated albumin endocytosis in renal proximal tubule-derived epithelial cells from opossum
Receptor-mediated endocytosis is an important mechanism for transport of macromolecules and regulation of cell-surface receptor expression. In renal proximal tubules, receptor-mediated endocytosis mediates the reabsorption of filtered albumin. Acidification of the endocytic compartments is essential...
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| Veröffentlicht in: | The Journal of physiology 1999-11, Vol.520 (3), p.709-721 |
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| creator | Gekle, Michael Drumm, Karina Mildenberger, Sigrid Freudinger, Ruth Gaßner, Birgit Silbernagl, Stefan |
| description | Receptor-mediated endocytosis is an important mechanism for transport of macromolecules and regulation of cell-surface receptor
expression. In renal proximal tubules, receptor-mediated endocytosis mediates the reabsorption of filtered albumin. Acidification
of the endocytic compartments is essential because it interferes with ligand-receptor dissociation, vesicle trafficking, fusion
events and coat formation.
Here we show that the activity of Na + âH + exchanger isoform 3 (NHE3) is important for proper receptor-mediated endocytosis of albumin and endosomal pH homeostasis
in a renal proximal tubular cell line (opossum kidney cells) which expresses NHE3 only.
Depending on their inhibitory potency with respect to NHE3 and their lipophilicity, the NHE inhibitors EIPA, amiloride and
HOE694 differentially reduced albumin endocytosis. The hydrophilic inhibitor HOE642 had no effect.
Inhibition of NHE3 led to an alkalinization of early endosomes and to an acidification of the cytoplasm, indicating that Na + âH + exchange contributes to the acidification of the early endosomal compartment due to the existence of a sufficient Na + gradient across the endosomal membrane.
Exclusive acidification of the cytoplasm with propionic acid or by removal of Na + induced a significantly smaller reduction in endocytosis than that induced by inhibition of Na + âH + exchange.
Analysis of the inhibitory profiles indicates that in early endosomes and endocytic vesicles NHE3 is of major importance,
whereas plasma membrane NHE3 plays a minor role.
Thus, NHE3-mediated acidification along the first part of the endocytic pathway plays an important role in receptor-mediated
endocytosis. Furthermore, the involvement of NHE3 offers new ways to explain the regulation of receptor-mediated endocytosis. |
| doi_str_mv | 10.1111/j.1469-7793.1999.00709.x |
| format | Article |
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expression. In renal proximal tubules, receptor-mediated endocytosis mediates the reabsorption of filtered albumin. Acidification
of the endocytic compartments is essential because it interferes with ligand-receptor dissociation, vesicle trafficking, fusion
events and coat formation.
Here we show that the activity of Na + âH + exchanger isoform 3 (NHE3) is important for proper receptor-mediated endocytosis of albumin and endosomal pH homeostasis
in a renal proximal tubular cell line (opossum kidney cells) which expresses NHE3 only.
Depending on their inhibitory potency with respect to NHE3 and their lipophilicity, the NHE inhibitors EIPA, amiloride and
HOE694 differentially reduced albumin endocytosis. The hydrophilic inhibitor HOE642 had no effect.
Inhibition of NHE3 led to an alkalinization of early endosomes and to an acidification of the cytoplasm, indicating that Na + âH + exchange contributes to the acidification of the early endosomal compartment due to the existence of a sufficient Na + gradient across the endosomal membrane.
Exclusive acidification of the cytoplasm with propionic acid or by removal of Na + induced a significantly smaller reduction in endocytosis than that induced by inhibition of Na + âH + exchange.
Analysis of the inhibitory profiles indicates that in early endosomes and endocytic vesicles NHE3 is of major importance,
whereas plasma membrane NHE3 plays a minor role.
Thus, NHE3-mediated acidification along the first part of the endocytic pathway plays an important role in receptor-mediated
endocytosis. Furthermore, the involvement of NHE3 offers new ways to explain the regulation of receptor-mediated endocytosis.</description><identifier>ISSN: 0022-3751</identifier><identifier>EISSN: 1469-7793</identifier><identifier>DOI: 10.1111/j.1469-7793.1999.00709.x</identifier><identifier>PMID: 10545138</identifier><language>eng</language><publisher>Oxford, UK: The Physiological Society</publisher><subject>Amiloride - analogs & derivatives ; Amiloride - pharmacology ; Animals ; Binding Sites - drug effects ; Cell Membrane - metabolism ; Cytosol - drug effects ; Cytosol - metabolism ; Endocytosis - drug effects ; Endocytosis - physiology ; Endosomes - drug effects ; Endosomes - metabolism ; Epithelial Cells - physiology ; Guanidines - pharmacology ; Hydrogen-Ion Concentration - drug effects ; Kidney Tubules, Proximal - cytology ; Kidney Tubules, Proximal - physiology ; Lysosomes - drug effects ; Lysosomes - metabolism ; Opossums ; Original ; Propionates - pharmacology ; Receptors, Cell Surface - physiology ; Serum Albumin - metabolism ; Sodium - metabolism ; Sodium-Hydrogen Exchangers - antagonists & inhibitors ; Sulfones - pharmacology</subject><ispartof>The Journal of physiology, 1999-11, Vol.520 (3), p.709-721</ispartof><rights>1999 The Journal of Physiology © 1999 The Physiological Society</rights><rights>The Physiological Society 1999 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5679-b0c26c2f9c36ab47c8a569a24111e7dc42627e974e30796152b65b3c9d0819d43</citedby><cites>FETCH-LOGICAL-c5679-b0c26c2f9c36ab47c8a569a24111e7dc42627e974e30796152b65b3c9d0819d43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2269612/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2269612/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10545138$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gekle, Michael</creatorcontrib><creatorcontrib>Drumm, Karina</creatorcontrib><creatorcontrib>Mildenberger, Sigrid</creatorcontrib><creatorcontrib>Freudinger, Ruth</creatorcontrib><creatorcontrib>Gaßner, Birgit</creatorcontrib><creatorcontrib>Silbernagl, Stefan</creatorcontrib><title>Inhibition of Na+âH+ exchange impairs receptor-mediated albumin endocytosis in renal proximal tubule-derived epithelial cells from opossum</title><title>The Journal of physiology</title><addtitle>J Physiol</addtitle><description>Receptor-mediated endocytosis is an important mechanism for transport of macromolecules and regulation of cell-surface receptor
expression. In renal proximal tubules, receptor-mediated endocytosis mediates the reabsorption of filtered albumin. Acidification
of the endocytic compartments is essential because it interferes with ligand-receptor dissociation, vesicle trafficking, fusion
events and coat formation.
Here we show that the activity of Na + âH + exchanger isoform 3 (NHE3) is important for proper receptor-mediated endocytosis of albumin and endosomal pH homeostasis
in a renal proximal tubular cell line (opossum kidney cells) which expresses NHE3 only.
Depending on their inhibitory potency with respect to NHE3 and their lipophilicity, the NHE inhibitors EIPA, amiloride and
HOE694 differentially reduced albumin endocytosis. The hydrophilic inhibitor HOE642 had no effect.
Inhibition of NHE3 led to an alkalinization of early endosomes and to an acidification of the cytoplasm, indicating that Na + âH + exchange contributes to the acidification of the early endosomal compartment due to the existence of a sufficient Na + gradient across the endosomal membrane.
Exclusive acidification of the cytoplasm with propionic acid or by removal of Na + induced a significantly smaller reduction in endocytosis than that induced by inhibition of Na + âH + exchange.
Analysis of the inhibitory profiles indicates that in early endosomes and endocytic vesicles NHE3 is of major importance,
whereas plasma membrane NHE3 plays a minor role.
Thus, NHE3-mediated acidification along the first part of the endocytic pathway plays an important role in receptor-mediated
endocytosis. Furthermore, the involvement of NHE3 offers new ways to explain the regulation of receptor-mediated endocytosis.</description><subject>Amiloride - analogs & derivatives</subject><subject>Amiloride - pharmacology</subject><subject>Animals</subject><subject>Binding Sites - drug effects</subject><subject>Cell Membrane - metabolism</subject><subject>Cytosol - drug effects</subject><subject>Cytosol - metabolism</subject><subject>Endocytosis - drug effects</subject><subject>Endocytosis - physiology</subject><subject>Endosomes - drug effects</subject><subject>Endosomes - metabolism</subject><subject>Epithelial Cells - physiology</subject><subject>Guanidines - pharmacology</subject><subject>Hydrogen-Ion Concentration - drug effects</subject><subject>Kidney Tubules, Proximal - cytology</subject><subject>Kidney Tubules, Proximal - physiology</subject><subject>Lysosomes - drug effects</subject><subject>Lysosomes - metabolism</subject><subject>Opossums</subject><subject>Original</subject><subject>Propionates - pharmacology</subject><subject>Receptors, Cell Surface - physiology</subject><subject>Serum Albumin - metabolism</subject><subject>Sodium - metabolism</subject><subject>Sodium-Hydrogen Exchangers - antagonists & inhibitors</subject><subject>Sulfones - pharmacology</subject><issn>0022-3751</issn><issn>1469-7793</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUU1u1DAUthCIDoUrIK9gUSXYTmLHEkJCFdCiCliUteU4LxOPkjjYSTtzA3ZIHIGjlIvhkKoqO7zxs76f954_hDAlKY3n1S6lOZeJEDJLqZQyJUQQme4foM0d8BBtCGEsyURBj9CTEHaE0IxI-RgdUVLkBc3KDfpxPrS2spN1A3YN_qRPfv-6-X7z8-wEw960etgCtv2orQ_Yg4Fxcj7pobZ6ghrrrpp7O2AYamcOkws24Pj0MOgOj97tbR-Laa7mDpIavL2KIhjt1EJnI2Kg6wJuvOuxG10Ic_8UPWp0F-DZ7X2Mvr5_d3l6llx8_nB--vYiMQUXMqmIYdywRpqM6yoXptQFl5rl8XdA1CZnnAmQIoeMCMlpwSpeVJmRNSmprPPsGL1Zfce5iusYGCavOzX6OLE_KKet-hcZbKu27koxxqMfiwYvbg28-zZDmFRvw7KPHsDNQXHJWMkkjcRyJRofN_TQ3DWhRC1pqp1aQlNLaGpJU_1NU-2j9Pn9Ie8J1_gi4fVKuLYdHP7bWF1-_BKLKH-5ylu7ba-tBzW2h2BdcMbCdFAFIypTC_MPZUjB0g</recordid><startdate>19991101</startdate><enddate>19991101</enddate><creator>Gekle, Michael</creator><creator>Drumm, Karina</creator><creator>Mildenberger, Sigrid</creator><creator>Freudinger, Ruth</creator><creator>Gaßner, Birgit</creator><creator>Silbernagl, Stefan</creator><general>The Physiological Society</general><general>Blackwell Science Ltd</general><general>Blackwell Science Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19991101</creationdate><title>Inhibition of Na+âH+ exchange impairs receptor-mediated albumin endocytosis in renal proximal tubule-derived epithelial cells from opossum</title><author>Gekle, Michael ; Drumm, Karina ; Mildenberger, Sigrid ; Freudinger, Ruth ; Gaßner, Birgit ; Silbernagl, Stefan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5679-b0c26c2f9c36ab47c8a569a24111e7dc42627e974e30796152b65b3c9d0819d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Amiloride - analogs & derivatives</topic><topic>Amiloride - pharmacology</topic><topic>Animals</topic><topic>Binding Sites - drug effects</topic><topic>Cell Membrane - metabolism</topic><topic>Cytosol - drug effects</topic><topic>Cytosol - metabolism</topic><topic>Endocytosis - drug effects</topic><topic>Endocytosis - physiology</topic><topic>Endosomes - drug effects</topic><topic>Endosomes - metabolism</topic><topic>Epithelial Cells - physiology</topic><topic>Guanidines - pharmacology</topic><topic>Hydrogen-Ion Concentration - drug effects</topic><topic>Kidney Tubules, Proximal - cytology</topic><topic>Kidney Tubules, Proximal - physiology</topic><topic>Lysosomes - drug effects</topic><topic>Lysosomes - metabolism</topic><topic>Opossums</topic><topic>Original</topic><topic>Propionates - pharmacology</topic><topic>Receptors, Cell Surface - physiology</topic><topic>Serum Albumin - metabolism</topic><topic>Sodium - metabolism</topic><topic>Sodium-Hydrogen Exchangers - antagonists & inhibitors</topic><topic>Sulfones - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gekle, Michael</creatorcontrib><creatorcontrib>Drumm, Karina</creatorcontrib><creatorcontrib>Mildenberger, Sigrid</creatorcontrib><creatorcontrib>Freudinger, Ruth</creatorcontrib><creatorcontrib>Gaßner, Birgit</creatorcontrib><creatorcontrib>Silbernagl, Stefan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gekle, Michael</au><au>Drumm, Karina</au><au>Mildenberger, Sigrid</au><au>Freudinger, Ruth</au><au>Gaßner, Birgit</au><au>Silbernagl, Stefan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Na+âH+ exchange impairs receptor-mediated albumin endocytosis in renal proximal tubule-derived epithelial cells from opossum</atitle><jtitle>The Journal of physiology</jtitle><addtitle>J Physiol</addtitle><date>1999-11-01</date><risdate>1999</risdate><volume>520</volume><issue>3</issue><spage>709</spage><epage>721</epage><pages>709-721</pages><issn>0022-3751</issn><eissn>1469-7793</eissn><abstract>Receptor-mediated endocytosis is an important mechanism for transport of macromolecules and regulation of cell-surface receptor
expression. In renal proximal tubules, receptor-mediated endocytosis mediates the reabsorption of filtered albumin. Acidification
of the endocytic compartments is essential because it interferes with ligand-receptor dissociation, vesicle trafficking, fusion
events and coat formation.
Here we show that the activity of Na + âH + exchanger isoform 3 (NHE3) is important for proper receptor-mediated endocytosis of albumin and endosomal pH homeostasis
in a renal proximal tubular cell line (opossum kidney cells) which expresses NHE3 only.
Depending on their inhibitory potency with respect to NHE3 and their lipophilicity, the NHE inhibitors EIPA, amiloride and
HOE694 differentially reduced albumin endocytosis. The hydrophilic inhibitor HOE642 had no effect.
Inhibition of NHE3 led to an alkalinization of early endosomes and to an acidification of the cytoplasm, indicating that Na + âH + exchange contributes to the acidification of the early endosomal compartment due to the existence of a sufficient Na + gradient across the endosomal membrane.
Exclusive acidification of the cytoplasm with propionic acid or by removal of Na + induced a significantly smaller reduction in endocytosis than that induced by inhibition of Na + âH + exchange.
Analysis of the inhibitory profiles indicates that in early endosomes and endocytic vesicles NHE3 is of major importance,
whereas plasma membrane NHE3 plays a minor role.
Thus, NHE3-mediated acidification along the first part of the endocytic pathway plays an important role in receptor-mediated
endocytosis. Furthermore, the involvement of NHE3 offers new ways to explain the regulation of receptor-mediated endocytosis.</abstract><cop>Oxford, UK</cop><pub>The Physiological Society</pub><pmid>10545138</pmid><doi>10.1111/j.1469-7793.1999.00709.x</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Journals; Wiley Online Library Free Content; IngentaConnect Free/Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Amiloride - analogs & derivatives Amiloride - pharmacology Animals Binding Sites - drug effects Cell Membrane - metabolism Cytosol - drug effects Cytosol - metabolism Endocytosis - drug effects Endocytosis - physiology Endosomes - drug effects Endosomes - metabolism Epithelial Cells - physiology Guanidines - pharmacology Hydrogen-Ion Concentration - drug effects Kidney Tubules, Proximal - cytology Kidney Tubules, Proximal - physiology Lysosomes - drug effects Lysosomes - metabolism Opossums Original Propionates - pharmacology Receptors, Cell Surface - physiology Serum Albumin - metabolism Sodium - metabolism Sodium-Hydrogen Exchangers - antagonists & inhibitors Sulfones - pharmacology |
| title | Inhibition of Na+âH+ exchange impairs receptor-mediated albumin endocytosis in renal proximal tubule-derived epithelial cells from opossum |
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