N-Glycan Branching Affects the Subcellular Distribution of and Inhibition of Matriptase by HAI-2/Placental Bikunin
The gene product of SPINT 2, that encodes a transmembrane, Kunitz-type serine protease inhibitor independently designated as HAI-2 or placenta bikunin (PB), is involved in regulation of sodium absorption in human gastrointestinal track. Here, we show that SPINT 2 is expressed as two species of diffe...
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| creator | Lai, Ying-Jung J Chang, Hsiang-Hua D Lai, Hongyu Xu, Yuan Shiao, Frank Huang, Nanxi Li, Linpei Lee, Ming-Shyue Johnson, Michael D Wang, Jehng-Kang Lin, Chen-Yong |
| description | The gene product of SPINT 2, that encodes a transmembrane, Kunitz-type serine protease inhibitor independently designated as HAI-2 or placenta bikunin (PB), is involved in regulation of sodium absorption in human gastrointestinal track. Here, we show that SPINT 2 is expressed as two species of different size (30-40- versus 25-kDa) due to different N-glycans on Asn-57. The N-glycan on 25-kDa HAI-2 appears to be of the oligomannose type and that on 30-40-kDa HAI-2 to be of complex type with extensive terminal N-acetylglucosamine branching. The two different types of N-glycan differentially mask two epitopes on HAI-2 polypeptide, recognized by two different HAI-2 mAbs. The 30-40-kDa form may be mature HAI-2, and is primarily localized in vesicles/granules. The 25-kDa form is likely immature HAI-2, that remains in the endoplasmic reticulum (ER) in the perinuclear regions of mammary epithelial cells. The two different N-glycans could, therefore, represent different maturation stages of N-glycosylation with the 25-kDa likely a precursor of the 30-40-kDa HAI-2, with the ratio of their levels roughly similar among a variety of cells. In breast cancer cells, a significant amount of the 30-40-kDa HAI-2 can translocate to and inhibit matriptase on the cell surface, followed by shedding of the matriptase-HAI-2 complex. The 25-kDa HAI-2 appears to have also exited the ER/Golgi, being localized at the cytoplasmic face of the plasma membrane of breast cancer cells. While the 25-kDa HAI-2 was also detected at the extracellular face of plasma membrane at very low levels it appears to have no role in matriptase inhibition probably due to its paucity on the cell surface. Our study reveals that N-glycan branching regulates HAI-2 through different subcellular distribution and subsequently access to different target proteases. |
| doi_str_mv | 10.1371/journal.pone.0132163 |
| format | Article |
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Here, we show that SPINT 2 is expressed as two species of different size (30-40- versus 25-kDa) due to different N-glycans on Asn-57. The N-glycan on 25-kDa HAI-2 appears to be of the oligomannose type and that on 30-40-kDa HAI-2 to be of complex type with extensive terminal N-acetylglucosamine branching. The two different types of N-glycan differentially mask two epitopes on HAI-2 polypeptide, recognized by two different HAI-2 mAbs. The 30-40-kDa form may be mature HAI-2, and is primarily localized in vesicles/granules. The 25-kDa form is likely immature HAI-2, that remains in the endoplasmic reticulum (ER) in the perinuclear regions of mammary epithelial cells. The two different N-glycans could, therefore, represent different maturation stages of N-glycosylation with the 25-kDa likely a precursor of the 30-40-kDa HAI-2, with the ratio of their levels roughly similar among a variety of cells. In breast cancer cells, a significant amount of the 30-40-kDa HAI-2 can translocate to and inhibit matriptase on the cell surface, followed by shedding of the matriptase-HAI-2 complex. The 25-kDa HAI-2 appears to have also exited the ER/Golgi, being localized at the cytoplasmic face of the plasma membrane of breast cancer cells. While the 25-kDa HAI-2 was also detected at the extracellular face of plasma membrane at very low levels it appears to have no role in matriptase inhibition probably due to its paucity on the cell surface. Our study reveals that N-glycan branching regulates HAI-2 through different subcellular distribution and subsequently access to different target proteases.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0132163</identifier><identifier>PMID: 26171609</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Amino Acid Sequence ; Bikunin ; Biochemistry ; Breast cancer ; Cancer ; Cell Line, Tumor ; Cell Membrane - metabolism ; Cell surface ; Endoplasmic reticulum ; Epithelial cells ; Epitopes ; Female ; Gas absorption ; Gastric cancer ; Gene Expression Regulation ; Glycan ; Glycosylation ; Golgi apparatus ; Growth factors ; Humans ; Hypotheses ; Inhibition ; Intracellular Space - metabolism ; Mammary gland ; Membrane Glycoproteins - chemistry ; Membrane Glycoproteins - metabolism ; Membrane Proteins - metabolism ; Molecular Sequence Data ; Molecular Weight ; Mutation ; N-Acetylglucosamine ; N-glycans ; Oncology ; Placenta ; Polysaccharides ; Polysaccharides - chemistry ; Pregnancy ; Proteases ; Protein Transport ; Rodents ; Serine ; Serine Endopeptidases - metabolism ; Serine proteinase ; Shedding ; Sodium ; Stomach cancer</subject><ispartof>PloS one, 2015-07, Vol.10 (7), p.e0132163-e0132163</ispartof><rights>2015 Lai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Lai et al 2015 Lai et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c592t-29be12bdaa52f71e60fc70c3d9dcfce62ece47e220c36b0efdd93745433f09d23</citedby><cites>FETCH-LOGICAL-c592t-29be12bdaa52f71e60fc70c3d9dcfce62ece47e220c36b0efdd93745433f09d23</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/PMC4501743/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501743/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26171609$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Saleem, Mohammad</contributor><creatorcontrib>Lai, Ying-Jung J</creatorcontrib><creatorcontrib>Chang, Hsiang-Hua D</creatorcontrib><creatorcontrib>Lai, Hongyu</creatorcontrib><creatorcontrib>Xu, Yuan</creatorcontrib><creatorcontrib>Shiao, Frank</creatorcontrib><creatorcontrib>Huang, Nanxi</creatorcontrib><creatorcontrib>Li, Linpei</creatorcontrib><creatorcontrib>Lee, Ming-Shyue</creatorcontrib><creatorcontrib>Johnson, Michael D</creatorcontrib><creatorcontrib>Wang, Jehng-Kang</creatorcontrib><creatorcontrib>Lin, Chen-Yong</creatorcontrib><title>N-Glycan Branching Affects the Subcellular Distribution of and Inhibition of Matriptase by HAI-2/Placental Bikunin</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The gene product of SPINT 2, that encodes a transmembrane, Kunitz-type serine protease inhibitor independently designated as HAI-2 or placenta bikunin (PB), is involved in regulation of sodium absorption in human gastrointestinal track. 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Our study reveals that N-glycan branching regulates HAI-2 through different subcellular distribution and subsequently access to different target proteases.</description><subject>Amino Acid Sequence</subject><subject>Bikunin</subject><subject>Biochemistry</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Cell Membrane - metabolism</subject><subject>Cell surface</subject><subject>Endoplasmic reticulum</subject><subject>Epithelial cells</subject><subject>Epitopes</subject><subject>Female</subject><subject>Gas absorption</subject><subject>Gastric cancer</subject><subject>Gene Expression Regulation</subject><subject>Glycan</subject><subject>Glycosylation</subject><subject>Golgi apparatus</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Inhibition</subject><subject>Intracellular Space - metabolism</subject><subject>Mammary gland</subject><subject>Membrane Glycoproteins - chemistry</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Membrane Proteins - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Molecular Weight</subject><subject>Mutation</subject><subject>N-Acetylglucosamine</subject><subject>N-glycans</subject><subject>Oncology</subject><subject>Placenta</subject><subject>Polysaccharides</subject><subject>Polysaccharides - chemistry</subject><subject>Pregnancy</subject><subject>Proteases</subject><subject>Protein Transport</subject><subject>Rodents</subject><subject>Serine</subject><subject>Serine Endopeptidases - metabolism</subject><subject>Serine proteinase</subject><subject>Shedding</subject><subject>Sodium</subject><subject>Stomach cancer</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUl1v0zAUjRCIbYV_gMASL7yk80fq1C9I3YCt0viQgGfrxrlpXVy7sxOk_vslazptiCdbx-ccn3t1suwNo1MmSna-CV304Ka74HFKmeBMimfZKVOC55JT8fzR_SQ7S2lD6UzMpXyZnXDJSiapOs3it_zK7Q14chHBm7X1K7JoGjRtIu0ayc-uMuhc5yCSTza10VZda4MnoSHga7L0a1vZI_IVesKuhYSk2pPrxTLn5z8cGPQtOHJh_3Te-lfZiwZcwtfjOcl-f_n86_I6v_l-tbxc3ORmpnibc1Uh41UNMONNyVDSxpTUiFrVpjEoORosSuS8x2RFsalrJcpiVgjRUFVzMcneHXx3LiQ9ritpJpXkheBC9ozlgVEH2OhdtFuIex3A6nsgxJWG2FrjUHNFOQqAuSpYYSoFTGK_XWHmiFCj6b0-jr911RbrYeQI7onp0xdv13oV_upiRlnZh55kH0aDGG47TK3e2jTsHjyG7j53yVnB6JD7_T_U_09XHFgmhpQiNg9hGNVDhY4qPVRIjxXqZW8fD_IgOnZG3AGgbcXZ</recordid><startdate>20150714</startdate><enddate>20150714</enddate><creator>Lai, Ying-Jung J</creator><creator>Chang, Hsiang-Hua D</creator><creator>Lai, Hongyu</creator><creator>Xu, Yuan</creator><creator>Shiao, Frank</creator><creator>Huang, Nanxi</creator><creator>Li, Linpei</creator><creator>Lee, Ming-Shyue</creator><creator>Johnson, Michael D</creator><creator>Wang, Jehng-Kang</creator><creator>Lin, Chen-Yong</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150714</creationdate><title>N-Glycan Branching Affects the Subcellular Distribution of and Inhibition of Matriptase by HAI-2/Placental Bikunin</title><author>Lai, Ying-Jung J ; Chang, Hsiang-Hua D ; Lai, Hongyu ; Xu, Yuan ; Shiao, Frank ; Huang, Nanxi ; Li, Linpei ; Lee, Ming-Shyue ; Johnson, Michael D ; Wang, Jehng-Kang ; Lin, Chen-Yong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c592t-29be12bdaa52f71e60fc70c3d9dcfce62ece47e220c36b0efdd93745433f09d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Amino Acid Sequence</topic><topic>Bikunin</topic><topic>Biochemistry</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cell Line, Tumor</topic><topic>Cell Membrane - metabolism</topic><topic>Cell surface</topic><topic>Endoplasmic reticulum</topic><topic>Epithelial cells</topic><topic>Epitopes</topic><topic>Female</topic><topic>Gas absorption</topic><topic>Gastric cancer</topic><topic>Gene Expression Regulation</topic><topic>Glycan</topic><topic>Glycosylation</topic><topic>Golgi apparatus</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Hypotheses</topic><topic>Inhibition</topic><topic>Intracellular Space - metabolism</topic><topic>Mammary gland</topic><topic>Membrane Glycoproteins - chemistry</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Membrane Proteins - metabolism</topic><topic>Molecular Sequence Data</topic><topic>Molecular Weight</topic><topic>Mutation</topic><topic>N-Acetylglucosamine</topic><topic>N-glycans</topic><topic>Oncology</topic><topic>Placenta</topic><topic>Polysaccharides</topic><topic>Polysaccharides - chemistry</topic><topic>Pregnancy</topic><topic>Proteases</topic><topic>Protein Transport</topic><topic>Rodents</topic><topic>Serine</topic><topic>Serine Endopeptidases - 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Here, we show that SPINT 2 is expressed as two species of different size (30-40- versus 25-kDa) due to different N-glycans on Asn-57. The N-glycan on 25-kDa HAI-2 appears to be of the oligomannose type and that on 30-40-kDa HAI-2 to be of complex type with extensive terminal N-acetylglucosamine branching. The two different types of N-glycan differentially mask two epitopes on HAI-2 polypeptide, recognized by two different HAI-2 mAbs. The 30-40-kDa form may be mature HAI-2, and is primarily localized in vesicles/granules. The 25-kDa form is likely immature HAI-2, that remains in the endoplasmic reticulum (ER) in the perinuclear regions of mammary epithelial cells. The two different N-glycans could, therefore, represent different maturation stages of N-glycosylation with the 25-kDa likely a precursor of the 30-40-kDa HAI-2, with the ratio of their levels roughly similar among a variety of cells. In breast cancer cells, a significant amount of the 30-40-kDa HAI-2 can translocate to and inhibit matriptase on the cell surface, followed by shedding of the matriptase-HAI-2 complex. The 25-kDa HAI-2 appears to have also exited the ER/Golgi, being localized at the cytoplasmic face of the plasma membrane of breast cancer cells. While the 25-kDa HAI-2 was also detected at the extracellular face of plasma membrane at very low levels it appears to have no role in matriptase inhibition probably due to its paucity on the cell surface. Our study reveals that N-glycan branching regulates HAI-2 through different subcellular distribution and subsequently access to different target proteases.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26171609</pmid><doi>10.1371/journal.pone.0132163</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1696243236 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Amino Acid Sequence Bikunin Biochemistry Breast cancer Cancer Cell Line, Tumor Cell Membrane - metabolism Cell surface Endoplasmic reticulum Epithelial cells Epitopes Female Gas absorption Gastric cancer Gene Expression Regulation Glycan Glycosylation Golgi apparatus Growth factors Humans Hypotheses Inhibition Intracellular Space - metabolism Mammary gland Membrane Glycoproteins - chemistry Membrane Glycoproteins - metabolism Membrane Proteins - metabolism Molecular Sequence Data Molecular Weight Mutation N-Acetylglucosamine N-glycans Oncology Placenta Polysaccharides Polysaccharides - chemistry Pregnancy Proteases Protein Transport Rodents Serine Serine Endopeptidases - metabolism Serine proteinase Shedding Sodium Stomach cancer |
| title | N-Glycan Branching Affects the Subcellular Distribution of and Inhibition of Matriptase by HAI-2/Placental Bikunin |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T23%3A40%3A19IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=N-Glycan%20Branching%20Affects%20the%20Subcellular%20Distribution%20of%20and%20Inhibition%20of%20Matriptase%20by%20HAI-2/Placental%20Bikunin&rft.jtitle=PloS%20one&rft.au=Lai,%20Ying-Jung%20J&rft.date=2015-07-14&rft.volume=10&rft.issue=7&rft.spage=e0132163&rft.epage=e0132163&rft.pages=e0132163-e0132163&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0132163&rft_dat=%3Cproquest_plos_%3E3743390611%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1696243236&rft_id=info:pmid/26171609&rft_doaj_id=oai_doaj_org_article_2902e3aa89414cb9a16e9323c8eeadec&rfr_iscdi=true |