PUBLICATION

The Sec domain protein Scfd1 facilitates trafficking of ECM components during chondrogenesis

Authors

Hou, N., Yang, Y., Scott, I.C., Lou, X.

ID

ZDB-PUB-161117-1

Date

2017

Source

Developmental Biology 421(1): 8-15 (Journal)

Registered Authors

Lou, Xin, Scott, Ian

Keywords

chondrogenesis, collagen, craniofacial development, intracellular transport, scfd1, zebrafish

MeSH Terms

Extracellular Matrix/metabolism*
Green Fluorescent Proteins/metabolism
Mice
Endoplasmic Reticulum Stress
Animals
Munc18 Proteins/chemistry*
Munc18 Proteins/metabolism*
Embryo, Nonmammalian/metabolism
Skull/embryology
Protein Transport
Face
Chondrogenesis*
Bone Development
Zebrafish/embryology
Zebrafish/metabolism*
Collagen Type II/metabolism
Qa-SNARE Proteins/metabolism
Immediate-Early Proteins/chemistry*
Immediate-Early Proteins/metabolism*
Protein Domains
Mutation/genetics
Chondrocytes/metabolism
Chondrocytes/pathology
Chondrocytes/ultrastructure
Unfolded Protein Response
Zebrafish Proteins/chemistry*
Zebrafish Proteins/metabolism*

PubMed

27851892 Full text @ Dev. Biol.

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.

Genes / Markers

Figures

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Expression

Fish	Conditions	Stage	Anatomy	Assay	Figure
scfd1^{nju201Gt/nju201Gt}	standard conditions	Protruding-mouth	pharyngeal arch	ISH	Fig. 4
scfd1^{nju201Gt/nju201Gt}	standard conditions	Pec-fin to Day 4	whole organism	RTPCR	Fig. 4
WT	standard conditions	Protruding-mouth	pharyngeal arch	ISH	Fig. 4
WT	standard conditions	Pec-fin to Day 4	whole organism	RTPCR	Fig. 4
scfd1^{nju201Gt/nju201Gt}	standard conditions	Protruding-mouth	mandibular arch skeleton chondrocyte	ISH	Fig. 3
scfd1^{nju201Gt/nju201Gt}	standard conditions	Day 4	mandibular arch skeleton chondrocyte	ISH	Fig. 3
WT	standard conditions	Day 4	mandibular arch skeleton chondrocyte	ISH	Fig. 3
WT	standard conditions	Protruding-mouth	mandibular arch skeleton chondrocyte	ISH	Fig. 3
scfd1^{nju201Gt/nju201Gt}	standard conditions	Protruding-mouth	pharyngeal arch	ISH	Fig. 4
scfd1^{nju201Gt/nju201Gt}	standard conditions	Pec-fin to Day 4	whole organism	RTPCR	Fig. 4

1 - 10 of 60

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
scfd1^{nju201Gt/nju201Gt}	standard conditions	Prim-25	whole organism scfd1 expression decreased amount, abnormal	Fig. S4
scfd1^{nju201Gt/nju201Gt}	standard conditions	Long-pec	whole organism scfd1 expression decreased amount, abnormal	Fig. S4
scfd1^{nju201Gt/nju201Gt}	standard conditions	Long-pec	whole organism morphology, normal	Fig. 2
scfd1^{nju201Gt/nju201Gt}	standard conditions	Pec-fin to Day 4	endoplasmic reticulum unfolded protein response increased occurrence, abnormal	Fig. 4
scfd1^{nju201Gt/nju201Gt}	standard conditions	Pec-fin to Day 4	whole organism ddit3 expression increased amount, abnormal	Fig. 4
scfd1^{nju201Gt/nju201Gt}	standard conditions	Pec-fin to Day 4	whole organism edem1 expression increased amount, abnormal	Fig. 4
scfd1^{nju201Gt/nju201Gt}	standard conditions	Pec-fin to Day 4	whole organism hspa5 expression increased amount, abnormal	Fig. 4
scfd1^{nju201Gt/nju201Gt}	standard conditions	Pec-fin to Day 4	whole organism syvn1 expression increased amount, abnormal	Fig. 4
scfd1^{nju201Gt/nju201Gt}	standard conditions	Pec-fin to Day 4	whole organism trib3 expression increased amount, abnormal	Fig. 4
scfd1^{nju201Gt/nju201Gt}	standard conditions	Protruding-mouth	chondrocyte vesicle ab1-col2a labeling mislocalised, abnormal	Fig. 3

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ir937Tg	Tg(-7.2sox10:EGFP)	Transgenic Insertion
nju201Gt	Gt(LOXP-GFP,LOXP:GFP)	Transgenic Insertion	scfd1
nju202Tg	Tg(hsp70l:scfd1,cryaa:EGFP)	Transgenic Insertion

1 - 3 of 3

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Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
scfd1^{nju201Gt/nju201Gt}
scfd1^{nju201Gt/nju201Gt}; nju202Tg
WT

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-col2a	monoclonal		IgG1	Mouse

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GFP	EFG	GFP

Mapping

Hou et al., 2017 ZDB-PUB-161117-1 PMID:27851892

The Sec domain protein Scfd1 facilitates trafficking of ECM components during chondrogenesis

Hou et al., 2017

ZDB-PUB-161117-1
PMID:27851892