title: The Sec domain protein Scfd1 facilitates trafficking of ECM components during chondrogenesis.
abstract: Chondrogenesis in the developing skeleton requires transformation of chondrocytes from a simple mesenchymal condensation to cells with a highly enriched extracellular matrix (ECM). This transition is in part accomplished by alterations in the chondrocyte protein transport machinery to cope with both the increased amount and large size of ECM components. In a zebrafish mutagenesis screen to identify genes essential for cartilage development, we uncovered a mutant that disrupts the gene encoding Sec1 family domain containing 1 (scfd1). Homozygous scfd1 mutant embryos exhibit a profound craniofacial abnormality caused by a failure of chondrogenesis. Loss of scfd1 was found to hinder ER to Golgi transport of ECM proteins and is accompanied with activation of the unfolded protein response in chondrocytes. We further demonstrate a conserved role for Scfd1 in differentiation of mammalian chondrocytes, in which loss of either SCFD1 or STX18, a SLY1 interacting t-SNARE, severely impair transport of type II collagen. These results show that the existence of a specific export pathway, mediated by a complex containing SCFD1 and STX18 that plays an essential role in secretion of large ECM proteins during chondrogenesis.
authors.affiliation: Model Animal Research Center, Nanjing University, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Hou
authors.affiliation: Model Animal Research Center, Nanjing University, China.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Canada; Department of Molecular Genetics, University of Toronto, Canada.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Scott
authors.affiliation: Model Animal Research Center, Nanjing University, China. Electronic address: xin.lou@nju.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Lou
mesh_terms: D000818:Animals; D001846:Bone Development; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D020219:Chondrogenesis; D024043:Collagen Type II / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D005109:Extracellular Matrix / Q000378:metabolism*; D005145:Face; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D051938:Munc18 Proteins / Q000737:chemistry* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D000072417:Protein Domains; D021381:Protein Transport; D050765:Qa-SNARE Proteins / Q000378:metabolism; D012886:Skull / Q000196:embryology; D056811:Unfolded Protein Response; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D024043:Collagen Type II; D017874:Immediate-Early Proteins; D051938:Munc18 Proteins; D050765:Qa-SNARE Proteins; C000619977:Scfd1 protein, zebrafish; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins
keywords: Chondrogenesis; Collagen; Craniofacial development; Intracellular transport; Zebrafish; scfd1