Arginine‐ but not alanine‐rich carboxy‐termini trigger nuclear translocation of mutant keratin 10 in ichthyosis with confetti
Ichthyosis with confetti (IWC) is a genodermatosis associated with dominant‐negative variants in keratin 10 (KRT10) or keratin 1 (KRT1). These frameshift variants result in extended aberrant proteins, localized to the nucleus rather than the cytoplasm. This mislocalization is thought to occur as a r...
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creator | Renz, Patricia Imahorn, Elias Spoerri, Iris Aushev, Magomet March, Oliver P. Wariwoda, Hedwig Von Arb, Sarah Volz, Andreas Itin, Peter H. Reichelt, Julia Burger, Bettina |
description | Ichthyosis with confetti (IWC) is a genodermatosis associated with dominant‐negative variants in keratin 10 (KRT10) or keratin 1 (KRT1). These frameshift variants result in extended aberrant proteins, localized to the nucleus rather than the cytoplasm. This mislocalization is thought to occur as a result of the altered carboxy (C)‐terminus, from poly‐glycine to either a poly‐arginine or ‐alanine tail. Previous studies on the type of C‐terminus and subcellular localization of the respective mutant protein are divergent. In order to fully elucidate the pathomechanism of IWC, a greater understanding is critical. This study aimed to establish the consequences for localization and intermediate filament formation of altered keratin 10 (K10) C‐termini. To achieve this, plasmids expressing distinct KRT10 variants were generated. Sequences encoded all possible reading frames of the K10 C‐terminus as well as a nonsense variant. A keratinocyte line was transfected with these plasmids. Additionally, gene editing was utilized to introduce frameshift variants in exon 6 and exon 7 at the endogenous KRT10 locus. Cellular localization of aberrant K10 was observed via immunofluorescence using various antibodies. In each setting, immunofluorescence analysis demonstrated aberrant nuclear localization of K10 featuring an arginine‐rich C‐terminus. However, this was not observed with K10 featuring an alanine‐rich C‐terminus. Instead, the protein displayed cytoplasmic localization, consistent with wild‐type and truncated forms of K10. This study demonstrates that, of the various 3′ frameshift variants of KRT10, exclusively arginine‐rich C‐termini lead to nuclear localization of K10. |
doi_str_mv | 10.1111/jcmm.14727 |
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These frameshift variants result in extended aberrant proteins, localized to the nucleus rather than the cytoplasm. This mislocalization is thought to occur as a result of the altered carboxy (C)‐terminus, from poly‐glycine to either a poly‐arginine or ‐alanine tail. Previous studies on the type of C‐terminus and subcellular localization of the respective mutant protein are divergent. In order to fully elucidate the pathomechanism of IWC, a greater understanding is critical. This study aimed to establish the consequences for localization and intermediate filament formation of altered keratin 10 (K10) C‐termini. To achieve this, plasmids expressing distinct KRT10 variants were generated. Sequences encoded all possible reading frames of the K10 C‐terminus as well as a nonsense variant. A keratinocyte line was transfected with these plasmids. Additionally, gene editing was utilized to introduce frameshift variants in exon 6 and exon 7 at the endogenous KRT10 locus. Cellular localization of aberrant K10 was observed via immunofluorescence using various antibodies. In each setting, immunofluorescence analysis demonstrated aberrant nuclear localization of K10 featuring an arginine‐rich C‐terminus. However, this was not observed with K10 featuring an alanine‐rich C‐terminus. Instead, the protein displayed cytoplasmic localization, consistent with wild‐type and truncated forms of K10. This study demonstrates that, of the various 3′ frameshift variants of KRT10, exclusively arginine‐rich C‐termini lead to nuclear localization of K10.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.14727</identifier><identifier>PMID: 31638346</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Active Transport, Cell Nucleus - genetics ; Alanine ; Alanine - genetics ; Alanine - metabolism ; alanine‐rich C‐terminus ; Amino acids ; Arginine ; Arginine - genetics ; Arginine - metabolism ; arginine‐rich C‐terminus ; carboxy terminus ; Cell Line ; Cell Nucleus - genetics ; Cell Nucleus - metabolism ; Cytoplasm ; Exons - genetics ; Frameshift Mutation ; Genetic modification ; Genodermatosis ; Genome editing ; Glycine ; Green Fluorescent Proteins - genetics ; Green Fluorescent Proteins - metabolism ; Humans ; Ichthyosiform Erythroderma, Congenital - genetics ; Ichthyosiform Erythroderma, Congenital - metabolism ; Ichthyosiform Erythroderma, Congenital - pathology ; Ichthyosis ; ichthyosis with confetti ; Immunofluorescence ; Keratin ; keratin 10 ; Keratin-10 - chemistry ; Keratin-10 - genetics ; Keratin-10 - metabolism ; Keratinocytes - metabolism ; KRT10 ; Localization ; Microscopy, Confocal ; Mutation ; nuclear localization ; Nuclear transport ; Original ; Patients ; Plasmids ; Translocation</subject><ispartof>Journal of cellular and molecular medicine, 2019-12, Vol.23 (12), p.8442-8452</ispartof><rights>2019 The Authors. published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.</rights><rights>2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.</rights><rights>2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4487-43070c532a4b04fd3fa942e37187a9b0779f2144e8b6b99d00fcdd422de2c52b3</citedby><cites>FETCH-LOGICAL-c4487-43070c532a4b04fd3fa942e37187a9b0779f2144e8b6b99d00fcdd422de2c52b3</cites><orcidid>0000-0002-7686-0176</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850952/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850952/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1417,11562,27924,27925,45574,45575,46052,46476,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31638346$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Renz, Patricia</creatorcontrib><creatorcontrib>Imahorn, Elias</creatorcontrib><creatorcontrib>Spoerri, Iris</creatorcontrib><creatorcontrib>Aushev, Magomet</creatorcontrib><creatorcontrib>March, Oliver P.</creatorcontrib><creatorcontrib>Wariwoda, Hedwig</creatorcontrib><creatorcontrib>Von Arb, Sarah</creatorcontrib><creatorcontrib>Volz, Andreas</creatorcontrib><creatorcontrib>Itin, Peter H.</creatorcontrib><creatorcontrib>Reichelt, Julia</creatorcontrib><creatorcontrib>Burger, Bettina</creatorcontrib><title>Arginine‐ but not alanine‐rich carboxy‐termini trigger nuclear translocation of mutant keratin 10 in ichthyosis with confetti</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>Ichthyosis with confetti (IWC) is a genodermatosis associated with dominant‐negative variants in keratin 10 (KRT10) or keratin 1 (KRT1). These frameshift variants result in extended aberrant proteins, localized to the nucleus rather than the cytoplasm. This mislocalization is thought to occur as a result of the altered carboxy (C)‐terminus, from poly‐glycine to either a poly‐arginine or ‐alanine tail. Previous studies on the type of C‐terminus and subcellular localization of the respective mutant protein are divergent. In order to fully elucidate the pathomechanism of IWC, a greater understanding is critical. This study aimed to establish the consequences for localization and intermediate filament formation of altered keratin 10 (K10) C‐termini. To achieve this, plasmids expressing distinct KRT10 variants were generated. Sequences encoded all possible reading frames of the K10 C‐terminus as well as a nonsense variant. A keratinocyte line was transfected with these plasmids. Additionally, gene editing was utilized to introduce frameshift variants in exon 6 and exon 7 at the endogenous KRT10 locus. Cellular localization of aberrant K10 was observed via immunofluorescence using various antibodies. In each setting, immunofluorescence analysis demonstrated aberrant nuclear localization of K10 featuring an arginine‐rich C‐terminus. However, this was not observed with K10 featuring an alanine‐rich C‐terminus. Instead, the protein displayed cytoplasmic localization, consistent with wild‐type and truncated forms of K10. This study demonstrates that, of the various 3′ frameshift variants of KRT10, exclusively arginine‐rich C‐termini lead to nuclear localization of K10.</description><subject>Active Transport, Cell Nucleus - genetics</subject><subject>Alanine</subject><subject>Alanine - genetics</subject><subject>Alanine - metabolism</subject><subject>alanine‐rich C‐terminus</subject><subject>Amino acids</subject><subject>Arginine</subject><subject>Arginine - genetics</subject><subject>Arginine - metabolism</subject><subject>arginine‐rich C‐terminus</subject><subject>carboxy terminus</subject><subject>Cell Line</subject><subject>Cell Nucleus - genetics</subject><subject>Cell Nucleus - metabolism</subject><subject>Cytoplasm</subject><subject>Exons - genetics</subject><subject>Frameshift Mutation</subject><subject>Genetic modification</subject><subject>Genodermatosis</subject><subject>Genome editing</subject><subject>Glycine</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>Humans</subject><subject>Ichthyosiform Erythroderma, Congenital - genetics</subject><subject>Ichthyosiform Erythroderma, Congenital - metabolism</subject><subject>Ichthyosiform Erythroderma, Congenital - pathology</subject><subject>Ichthyosis</subject><subject>ichthyosis with confetti</subject><subject>Immunofluorescence</subject><subject>Keratin</subject><subject>keratin 10</subject><subject>Keratin-10 - chemistry</subject><subject>Keratin-10 - genetics</subject><subject>Keratin-10 - metabolism</subject><subject>Keratinocytes - metabolism</subject><subject>KRT10</subject><subject>Localization</subject><subject>Microscopy, Confocal</subject><subject>Mutation</subject><subject>nuclear localization</subject><subject>Nuclear transport</subject><subject>Original</subject><subject>Patients</subject><subject>Plasmids</subject><subject>Translocation</subject><issn>1582-1838</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU1uFDEQhS1EREJgwwGQJTYIaYL_um1vkKIRP4kSsYG15Xa7Zzx028F2E2aHxAU4IyehkhkiYIEXdlX509OzH0JPKDmhsF5u3DSdUCGZvIeOaKPYQmgu7u9rqrg6RA9L2RDCW8r1A3TIacsVF-0R-n6aVyGG6H9--4G7ueKYKraj3Y9ycGvsbO7S1y201ecJaFxzWK18xnF2o7cZehvLmJytIUWcBjzN1caKP_kMo4gpwbCDVl1vUwkFX4cKuikOvtbwCB0Mdiz-8f48Rh_fvP6wfLe4eP_2bHl6sXBCKLkQnEjiGs6s6IgYej5YLZjnkippdUek1AOjQnjVtZ3WPSGD63vBWO-Za1jHj9Grne7V3E2-dz6C79Fc5TDZvDXJBvP3TQxrs0pfTKsaohsGAs_3Ajl9nn2pZgrF-RG-y6e5GAYOJddaS0Cf_YNu0pwjPA8oyhUhrNFAvdhRLqdSsh_uzFBibrI1N9ma22wBfvqn_Tv0d5gA0B1wHUa__Y-UOV9eXu5EfwHvXLTD</recordid><startdate>201912</startdate><enddate>201912</enddate><creator>Renz, Patricia</creator><creator>Imahorn, Elias</creator><creator>Spoerri, Iris</creator><creator>Aushev, Magomet</creator><creator>March, Oliver P.</creator><creator>Wariwoda, Hedwig</creator><creator>Von Arb, Sarah</creator><creator>Volz, Andreas</creator><creator>Itin, Peter H.</creator><creator>Reichelt, Julia</creator><creator>Burger, Bettina</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><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>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7686-0176</orcidid></search><sort><creationdate>201912</creationdate><title>Arginine‐ but not alanine‐rich carboxy‐termini trigger nuclear translocation of mutant keratin 10 in ichthyosis with confetti</title><author>Renz, Patricia ; Imahorn, Elias ; Spoerri, Iris ; Aushev, Magomet ; March, Oliver P. ; Wariwoda, Hedwig ; Von Arb, Sarah ; Volz, Andreas ; Itin, Peter H. ; Reichelt, Julia ; Burger, Bettina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4487-43070c532a4b04fd3fa942e37187a9b0779f2144e8b6b99d00fcdd422de2c52b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Active Transport, Cell Nucleus - genetics</topic><topic>Alanine</topic><topic>Alanine - genetics</topic><topic>Alanine - metabolism</topic><topic>alanine‐rich C‐terminus</topic><topic>Amino acids</topic><topic>Arginine</topic><topic>Arginine - genetics</topic><topic>Arginine - metabolism</topic><topic>arginine‐rich C‐terminus</topic><topic>carboxy terminus</topic><topic>Cell Line</topic><topic>Cell Nucleus - genetics</topic><topic>Cell Nucleus - metabolism</topic><topic>Cytoplasm</topic><topic>Exons - genetics</topic><topic>Frameshift Mutation</topic><topic>Genetic modification</topic><topic>Genodermatosis</topic><topic>Genome editing</topic><topic>Glycine</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>Humans</topic><topic>Ichthyosiform Erythroderma, Congenital - genetics</topic><topic>Ichthyosiform Erythroderma, Congenital - metabolism</topic><topic>Ichthyosiform Erythroderma, Congenital - pathology</topic><topic>Ichthyosis</topic><topic>ichthyosis with confetti</topic><topic>Immunofluorescence</topic><topic>Keratin</topic><topic>keratin 10</topic><topic>Keratin-10 - chemistry</topic><topic>Keratin-10 - genetics</topic><topic>Keratin-10 - metabolism</topic><topic>Keratinocytes - metabolism</topic><topic>KRT10</topic><topic>Localization</topic><topic>Microscopy, Confocal</topic><topic>Mutation</topic><topic>nuclear localization</topic><topic>Nuclear transport</topic><topic>Original</topic><topic>Patients</topic><topic>Plasmids</topic><topic>Translocation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Renz, Patricia</creatorcontrib><creatorcontrib>Imahorn, Elias</creatorcontrib><creatorcontrib>Spoerri, Iris</creatorcontrib><creatorcontrib>Aushev, Magomet</creatorcontrib><creatorcontrib>March, Oliver P.</creatorcontrib><creatorcontrib>Wariwoda, Hedwig</creatorcontrib><creatorcontrib>Von Arb, Sarah</creatorcontrib><creatorcontrib>Volz, Andreas</creatorcontrib><creatorcontrib>Itin, Peter H.</creatorcontrib><creatorcontrib>Reichelt, Julia</creatorcontrib><creatorcontrib>Burger, Bettina</creatorcontrib><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Renz, Patricia</au><au>Imahorn, Elias</au><au>Spoerri, Iris</au><au>Aushev, Magomet</au><au>March, Oliver P.</au><au>Wariwoda, Hedwig</au><au>Von Arb, Sarah</au><au>Volz, Andreas</au><au>Itin, Peter H.</au><au>Reichelt, Julia</au><au>Burger, Bettina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Arginine‐ but not alanine‐rich carboxy‐termini trigger nuclear translocation of mutant keratin 10 in ichthyosis with confetti</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2019-12</date><risdate>2019</risdate><volume>23</volume><issue>12</issue><spage>8442</spage><epage>8452</epage><pages>8442-8452</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>Ichthyosis with confetti (IWC) is a genodermatosis associated with dominant‐negative variants in keratin 10 (KRT10) or keratin 1 (KRT1). These frameshift variants result in extended aberrant proteins, localized to the nucleus rather than the cytoplasm. This mislocalization is thought to occur as a result of the altered carboxy (C)‐terminus, from poly‐glycine to either a poly‐arginine or ‐alanine tail. Previous studies on the type of C‐terminus and subcellular localization of the respective mutant protein are divergent. In order to fully elucidate the pathomechanism of IWC, a greater understanding is critical. This study aimed to establish the consequences for localization and intermediate filament formation of altered keratin 10 (K10) C‐termini. To achieve this, plasmids expressing distinct KRT10 variants were generated. Sequences encoded all possible reading frames of the K10 C‐terminus as well as a nonsense variant. A keratinocyte line was transfected with these plasmids. Additionally, gene editing was utilized to introduce frameshift variants in exon 6 and exon 7 at the endogenous KRT10 locus. Cellular localization of aberrant K10 was observed via immunofluorescence using various antibodies. In each setting, immunofluorescence analysis demonstrated aberrant nuclear localization of K10 featuring an arginine‐rich C‐terminus. However, this was not observed with K10 featuring an alanine‐rich C‐terminus. Instead, the protein displayed cytoplasmic localization, consistent with wild‐type and truncated forms of K10. This study demonstrates that, of the various 3′ frameshift variants of KRT10, exclusively arginine‐rich C‐termini lead to nuclear localization of K10.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>31638346</pmid><doi>10.1111/jcmm.14727</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-7686-0176</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Active Transport, Cell Nucleus - genetics Alanine Alanine - genetics Alanine - metabolism alanine‐rich C‐terminus Amino acids Arginine Arginine - genetics Arginine - metabolism arginine‐rich C‐terminus carboxy terminus Cell Line Cell Nucleus - genetics Cell Nucleus - metabolism Cytoplasm Exons - genetics Frameshift Mutation Genetic modification Genodermatosis Genome editing Glycine Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism Humans Ichthyosiform Erythroderma, Congenital - genetics Ichthyosiform Erythroderma, Congenital - metabolism Ichthyosiform Erythroderma, Congenital - pathology Ichthyosis ichthyosis with confetti Immunofluorescence Keratin keratin 10 Keratin-10 - chemistry Keratin-10 - genetics Keratin-10 - metabolism Keratinocytes - metabolism KRT10 Localization Microscopy, Confocal Mutation nuclear localization Nuclear transport Original Patients Plasmids Translocation |
title | Arginine‐ but not alanine‐rich carboxy‐termini trigger nuclear translocation of mutant keratin 10 in ichthyosis with confetti |
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