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Here, we sought to determine how giantin impacts the production of healthy bone tissue by focusing on the main protein component of the osteoid, type I collagen. Giantin mutant zebrafish accumulate multiple spontaneous fractures in their caudal fin, suggesting their bones may be more brittle. Inducing new experimental fractures revealed defects in the mineralization of newly deposited collagen as well as diminished procollagen reporter expression in mutant fish. Analysis of a human giantin knockout cell line expressing a GFP-tagged procollagen showed that procollagen trafficking is independent of giantin. However, our data show that intracellular N-propeptide processing of pro-\u03b11(I) is defective in the absence of giantin. These data demonstrate a conserved role for giantin in collagen biosynthesis and extracellular matrix assembly. Our work also provides evidence of a giantin-dependent pathway for intracellular procollagen processing.<\/jats:p>","DOI":"10.1083\/jcb.202005166","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T02:22:23Z","timestamp":1615947743000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["Giantin is required for intracellular N-terminal processing of type I procollagen"],"prefix":"10.1083","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8967-7277","authenticated-orcid":true,"given":"Nicola L.","family":"Stevenson","sequence":"first","affiliation":[{"name":"Cell Biology Laboratories, School of Biochemistry, Faculty of Life Sciences, University of Bristol, Bristol, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7808-6121","authenticated-orcid":true,"given":"Dylan J.M.","family":"Bergen","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience, Faculty of Life Sciences, University of Bristol, Bristol, UK 2"},{"name":"Musculoskeletal Research Unit, Translational Health Sciences, University of Bristol, Bristol, UK 3"},{"name":"Bristol Medical School, Faculty of Health Sciences, University of Bristol, Southmead Hospital, Bristol, UK 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9034-0823","authenticated-orcid":true,"given":"Yinhui","family":"Lu","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK 5"},{"name":"Manchester Academic Health Science Centre, Manchester, UK 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0118-7586","authenticated-orcid":false,"given":"M. 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