{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:21:13Z","timestamp":1787008873948,"version":"build-2736575974"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD096030"],"award-info":[{"award-number":["HD096030"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD090156"],"award-info":[{"award-number":["HD090156"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Thrombospondin 1 (THBS1) is a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes. THBS1\u2019s diverse functions are attributed to interactions between the modular domains of THBS1 with an array of proteins found in the extracellular matrix. THBS1\u2019s three Thrombospondin type 1 repeats (TSRs) are modified with O-linked glucose-fucose disaccharide and C-mannose. It is unknown whether these modifications impact trafficking and\/or function of THBS1 in vivo. The O-fucose is added by Protein O-fucosyltransferase 2 (POFUT2) and is sequentially extended to the disaccharide by \u03b23glucosyltransferase (B3GLCT). The C-mannose is added by one or more of four C-mannosyltransferases. O-fucosylation by POFUT2\/B3GLCT in the endoplasmic reticulum has been proposed to play a role in quality control by locking TSR domains into their three-dimensional fold, allowing for proper secretion of many O-fucosylated substrates. Prior studies showed the siRNA knockdown of POFUT2 in HEK293T cells blocked secretion of TSRs 1\u20133 from THBS1. Here we demonstrated that secretion of THBS1 TSRs 1\u20133 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce the trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. Additionally, we demonstrated that all three TSRs from platelet THBS1 were highly C-mannosylated, which has been shown to stabilize TSRs in vitro. Combined, these results suggested that POFUT2 substrates with TSRs that are also modified by C-mannose may be less susceptible to trafficking defects resulting from the loss of the glucose-fucose disaccharide.<\/jats:p>","DOI":"10.1093\/glycob\/cwad006","type":"journal-article","created":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T00:37:11Z","timestamp":1674866231000},"page":"301-310","source":"Crossref","is-referenced-by-count":4,"title":["<i>O-<\/i>\n                    fucosylation of thrombospondin type I repeats is dispensable for trafficking thrombospondin 1 to platelet secretory granules"],"prefix":"10.1093","volume":"33","author":[{"given":"Steven J","family":"Berardinelli","sequence":"first","affiliation":[{"name":"Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, University of Georgia , Athens, GA 30602 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R","family":"Sillato","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Stony Brook University , Stony Brook, NY 11794 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C","family":"Grady","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Stony Brook University , Stony Brook, NY 11794 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjiv","family":"Neupane","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Stony Brook University , Stony Brook, NY 11794 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Ito","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, University of Georgia , Athens, GA 30602 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7439-9577","authenticated-orcid":false,"given":"Robert S","family":"Haltiwanger","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, University of Georgia , Athens, GA 30602 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4713-9264","authenticated-orcid":false,"given":"Bernadette C","family":"Holdener","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Stony Brook University , Stony Brook, NY 11794 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"issue":"4","key":"2023051716242740700_ref1","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/S0021-9258(17)49916-9","article-title":"C-mannosylation of toxoplasma 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