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Igβ ubiquitination activates PI3K signals required for endosomal sorting
A wealth of in vitro data has demonstrated a central role for receptor ubiquitination in endocytic sorting. However, how receptor ubiquitination functions in vivo is poorly understood. Herein, we report that ablation of B cell antigen receptor ubiquitination in vivo uncouples the receptor from CD19...
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| Published in: | The Journal of experimental medicine 2017-12, Vol.214 (12), p.3775-3790 |
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| Main Authors: | , , , , , , , , , , |
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| Language: | English |
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| container_end_page | 3790 |
| container_issue | 12 |
| container_start_page | 3775 |
| container_title | The Journal of experimental medicine |
| container_volume | 214 |
| creator | Veselits, Margaret Tanaka, Azusa Chen, Yaoqing Hamel, Keith Mandal, Malay Kandasamy, Matheswaran Manicassamy, Balaji O'Neill, Shannon K Wilson, Patrick Sciammas, Roger Clark, Marcus R |
| description | A wealth of in vitro data has demonstrated a central role for receptor ubiquitination in endocytic sorting. However, how receptor ubiquitination functions in vivo is poorly understood. Herein, we report that ablation of B cell antigen receptor ubiquitination in vivo uncouples the receptor from CD19 phosphorylation and phosphatidylinositol 3-kinase (PI3K) signals. These signals are necessary and sufficient for accumulating phosphatidylinositol (3,4,5)-trisphosphate (PIP
) on B cell receptor-containing early endosomes and proper sorting into the MHC class II antigen-presenting compartment (MIIC). Surprisingly, MIIC targeting is dispensable for T cell-dependent immunity. Rather, it is critical for activating endosomal toll-like receptors and antiviral humoral immunity. These findings demonstrate a novel mechanism of receptor endosomal signaling required for specific peripheral immune responses. |
| doi_str_mv | 10.1084/jem.20161868 |
| format | article |
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) on B cell receptor-containing early endosomes and proper sorting into the MHC class II antigen-presenting compartment (MIIC). Surprisingly, MIIC targeting is dispensable for T cell-dependent immunity. Rather, it is critical for activating endosomal toll-like receptors and antiviral humoral immunity. These findings demonstrate a novel mechanism of receptor endosomal signaling required for specific peripheral immune responses.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20161868</identifier><identifier>PMID: 29141870</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>1-Phosphatidylinositol 3-kinase ; Accumulation ; Antigen processing ; Antigens ; B-cell receptor ; CD19 antigen ; Compartments ; Endosomes ; Humoral immunity ; Immune response ; Immune system ; Immunity ; Lymphocytes B ; Lymphocytes T ; Major histocompatibility complex ; Membranes ; Phosphatidylinositol 3,4,5-triphosphate ; Phosphorylation ; Proteins ; Receptors ; Signaling ; T cell receptors ; Toll-like receptors ; Ubiquitination</subject><ispartof>The Journal of experimental medicine, 2017-12, Vol.214 (12), p.3775-3790</ispartof><rights>2017 Veselits et al.</rights><rights>Copyright Rockefeller University Press Dec 4, 2017</rights><rights>2017 Veselits et al. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-8e3c6671f4cda50c11d76ab742aa159ae0eb36faf4db22194ec93dd9425b04393</citedby><cites>FETCH-LOGICAL-c412t-8e3c6671f4cda50c11d76ab742aa159ae0eb36faf4db22194ec93dd9425b04393</cites><orcidid>0000-0001-8755-6260 ; 0000-0002-0451-3896</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/PMC5716028/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716028/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,27957,27958,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29141870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Veselits, Margaret</creatorcontrib><creatorcontrib>Tanaka, Azusa</creatorcontrib><creatorcontrib>Chen, Yaoqing</creatorcontrib><creatorcontrib>Hamel, Keith</creatorcontrib><creatorcontrib>Mandal, Malay</creatorcontrib><creatorcontrib>Kandasamy, Matheswaran</creatorcontrib><creatorcontrib>Manicassamy, Balaji</creatorcontrib><creatorcontrib>O'Neill, Shannon K</creatorcontrib><creatorcontrib>Wilson, Patrick</creatorcontrib><creatorcontrib>Sciammas, Roger</creatorcontrib><creatorcontrib>Clark, Marcus R</creatorcontrib><title>Igβ ubiquitination activates PI3K signals required for endosomal sorting</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>A wealth of in vitro data has demonstrated a central role for receptor ubiquitination in endocytic sorting. However, how receptor ubiquitination functions in vivo is poorly understood. Herein, we report that ablation of B cell antigen receptor ubiquitination in vivo uncouples the receptor from CD19 phosphorylation and phosphatidylinositol 3-kinase (PI3K) signals. These signals are necessary and sufficient for accumulating phosphatidylinositol (3,4,5)-trisphosphate (PIP
) on B cell receptor-containing early endosomes and proper sorting into the MHC class II antigen-presenting compartment (MIIC). Surprisingly, MIIC targeting is dispensable for T cell-dependent immunity. Rather, it is critical for activating endosomal toll-like receptors and antiviral humoral immunity. These findings demonstrate a novel mechanism of receptor endosomal signaling required for specific peripheral immune responses.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Accumulation</subject><subject>Antigen processing</subject><subject>Antigens</subject><subject>B-cell receptor</subject><subject>CD19 antigen</subject><subject>Compartments</subject><subject>Endosomes</subject><subject>Humoral immunity</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunity</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Major histocompatibility complex</subject><subject>Membranes</subject><subject>Phosphatidylinositol 3,4,5-triphosphate</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Signaling</subject><subject>T cell receptors</subject><subject>Toll-like receptors</subject><subject>Ubiquitination</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNpd0ctKxDAUBuAgio6XnWspuHFhNSe3phtBxMvggC50HdI0HTO0jSbtgK_lg_hMZvCCusoiX35Ozo_QPuATwJKdLmx3QjAIkEKuoQlwhvOSU7mOJhgTkgPGxRbajnGBMTDGxSbaIiUwkAWeoOl0_v6WjZV7Gd3gej0432faDG6pBxuz-ym9zaKb97qNWbAJBVtnjQ-Z7WsffafbLPqQXs530UaTlN37OnfQ49Xlw8VNPru7nl6cz3LDgAy5tNQIUUDDTK05NgB1IXRVMKI18FJbbCsqGt2wuiIESmZNSeu6ZIRXmNGS7qCzz9znsepsbWw_BN2q5-A6HV6V1079vendk5r7peIFCExkCjj6Cgj-ZbRxUJ2Lxrat7q0fo4JScMILUfBED__RhR_DahlJScoo55ImdfypTPAxBtv8DANYrTpSqSP13VHiB78_8IO_S6EfQh6OXw</recordid><startdate>20171204</startdate><enddate>20171204</enddate><creator>Veselits, Margaret</creator><creator>Tanaka, Azusa</creator><creator>Chen, Yaoqing</creator><creator>Hamel, Keith</creator><creator>Mandal, Malay</creator><creator>Kandasamy, Matheswaran</creator><creator>Manicassamy, Balaji</creator><creator>O'Neill, Shannon K</creator><creator>Wilson, Patrick</creator><creator>Sciammas, Roger</creator><creator>Clark, Marcus R</creator><general>Rockefeller University Press</general><general>The Rockefeller University Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8755-6260</orcidid><orcidid>https://orcid.org/0000-0002-0451-3896</orcidid></search><sort><creationdate>20171204</creationdate><title>Igβ ubiquitination activates PI3K signals required for endosomal sorting</title><author>Veselits, Margaret ; Tanaka, Azusa ; Chen, Yaoqing ; Hamel, Keith ; Mandal, Malay ; Kandasamy, Matheswaran ; Manicassamy, Balaji ; O'Neill, Shannon K ; Wilson, Patrick ; Sciammas, Roger ; Clark, Marcus R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-8e3c6671f4cda50c11d76ab742aa159ae0eb36faf4db22194ec93dd9425b04393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Accumulation</topic><topic>Antigen processing</topic><topic>Antigens</topic><topic>B-cell receptor</topic><topic>CD19 antigen</topic><topic>Compartments</topic><topic>Endosomes</topic><topic>Humoral immunity</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunity</topic><topic>Lymphocytes B</topic><topic>Lymphocytes T</topic><topic>Major histocompatibility complex</topic><topic>Membranes</topic><topic>Phosphatidylinositol 3,4,5-triphosphate</topic><topic>Phosphorylation</topic><topic>Proteins</topic><topic>Receptors</topic><topic>Signaling</topic><topic>T cell receptors</topic><topic>Toll-like receptors</topic><topic>Ubiquitination</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Veselits, Margaret</creatorcontrib><creatorcontrib>Tanaka, Azusa</creatorcontrib><creatorcontrib>Chen, Yaoqing</creatorcontrib><creatorcontrib>Hamel, Keith</creatorcontrib><creatorcontrib>Mandal, Malay</creatorcontrib><creatorcontrib>Kandasamy, Matheswaran</creatorcontrib><creatorcontrib>Manicassamy, Balaji</creatorcontrib><creatorcontrib>O'Neill, Shannon K</creatorcontrib><creatorcontrib>Wilson, Patrick</creatorcontrib><creatorcontrib>Sciammas, Roger</creatorcontrib><creatorcontrib>Clark, Marcus R</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Veselits, Margaret</au><au>Tanaka, Azusa</au><au>Chen, Yaoqing</au><au>Hamel, Keith</au><au>Mandal, Malay</au><au>Kandasamy, Matheswaran</au><au>Manicassamy, Balaji</au><au>O'Neill, Shannon K</au><au>Wilson, Patrick</au><au>Sciammas, Roger</au><au>Clark, Marcus R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Igβ ubiquitination activates PI3K signals required for endosomal sorting</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>2017-12-04</date><risdate>2017</risdate><volume>214</volume><issue>12</issue><spage>3775</spage><epage>3790</epage><pages>3775-3790</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>A wealth of in vitro data has demonstrated a central role for receptor ubiquitination in endocytic sorting. However, how receptor ubiquitination functions in vivo is poorly understood. Herein, we report that ablation of B cell antigen receptor ubiquitination in vivo uncouples the receptor from CD19 phosphorylation and phosphatidylinositol 3-kinase (PI3K) signals. These signals are necessary and sufficient for accumulating phosphatidylinositol (3,4,5)-trisphosphate (PIP
) on B cell receptor-containing early endosomes and proper sorting into the MHC class II antigen-presenting compartment (MIIC). Surprisingly, MIIC targeting is dispensable for T cell-dependent immunity. Rather, it is critical for activating endosomal toll-like receptors and antiviral humoral immunity. These findings demonstrate a novel mechanism of receptor endosomal signaling required for specific peripheral immune responses.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>29141870</pmid><doi>10.1084/jem.20161868</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0001-8755-6260</orcidid><orcidid>https://orcid.org/0000-0002-0451-3896</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of experimental medicine, 2017-12, Vol.214 (12), p.3775-3790 |
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| subjects | 1-Phosphatidylinositol 3-kinase Accumulation Antigen processing Antigens B-cell receptor CD19 antigen Compartments Endosomes Humoral immunity Immune response Immune system Immunity Lymphocytes B Lymphocytes T Major histocompatibility complex Membranes Phosphatidylinositol 3,4,5-triphosphate Phosphorylation Proteins Receptors Signaling T cell receptors Toll-like receptors Ubiquitination |
| title | Igβ ubiquitination activates PI3K signals required for endosomal sorting |
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