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PMID:18713835

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Citation

Townley, AK, Feng, Y, Schmidt, K, Carter, DA, Porter, R, Verkade, P and Stephens, DJ (2008) Efficient coupling of Sec23-Sec24 to Sec13-Sec31 drives COPII-dependent collagen secretion and is essential for normal craniofacial development. J. Cell. Sci. 121:3025-34

Abstract

The COPII coat assembles on endoplasmic reticulum membranes to coordinate the collection of secretory cargo with the formation of transport vesicles. During COPII assembly, Sar1 deforms the membrane and recruits the Sec23-Sec24 complex (Sec23/24), which is the primary cargo-binding adaptor for the system, and Sec13-Sec31 (Sec13/31), which provides a structural outer layer for vesicle formation. Here we show that Sec13 depletion results in concomitant loss of Sec31 and juxtanuclear clustering of pre-budding complexes containing Sec23/24 and cargo. Electron microscopy reveals the presence of curved coated profiles on distended endoplasmic reticulum, indicating that Sec13/31 is not required for the generation or maintenance of the curvature. Surprisingly, export of tsO45-G-YFP, a marker of secretory cargo, is unaffected by Sec13/31 depletion; by contrast, secretion of collagen from primary fibroblasts is strongly inhibited. Suppression of Sec13 expression in zebrafish causes defects in proteoglycan deposition and skeletal abnormalities that are grossly similar to the craniofacial abnormalities of crusher mutant zebrafish and patients with cranio-lenticulo-sutural dysplasia. We conclude that efficient coupling of the inner (Sec23/24) and outer (Sec13/31) layers of the COPII coat is required to drive the export of collagen from the endoplasmic reticulum, and that highly efficient COPII assembly is essential for normal craniofacial development during embryogenesis.

Links

PubMed Online version:10.1242/jcs.031070

Keywords

Animals; COP-Coated Vesicles/metabolism; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cells, Cultured; Coatomer Protein/metabolism; Collagen/metabolism; Endoplasmic Reticulum/metabolism; Endoplasmic Reticulum/ultrastructure; Exocytosis/physiology; Facial Bones/embryology; Fibroblasts/cytology; Fibroblasts/metabolism; Humans; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Skull/embryology; Vesicular Transport Proteins/genetics; Vesicular Transport Proteins/metabolism; Zebrafish/anatomy & histology; Zebrafish/embryology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DANRE:A0A2R8RKG2

involved_in

GO:0006888: endoplasmic reticulum to Golgi vesicle-mediated transport

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P55735

P

Seeded From UniProt

complete

DANRE:A0A2R8RKG2

involved_in

GO:0051216: cartilage development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-090206-3,ZFIN:ZDB-MRPHLNO-090206-4

P

Seeded From UniProt

complete

DANRE:A0A2R8RKG2

involved_in

GO:0070278: extracellular matrix constituent secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-090206-3,ZFIN:ZDB-MRPHLNO-090206-4

P

Seeded From UniProt

complete

DANRE:Q7T2E1

involved_in

GO:0006888: endoplasmic reticulum to Golgi vesicle-mediated transport

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P55735

P

Seeded From UniProt

complete

DANRE:Q7T2E1

involved_in

GO:0051216: cartilage development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-090206-3,ZFIN:ZDB-MRPHLNO-090206-4

P

Seeded From UniProt

complete

DANRE:Q7T2E1

involved_in

GO:0070278: extracellular matrix constituent secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-090206-3,ZFIN:ZDB-MRPHLNO-090206-4

P

Seeded From UniProt

complete


See also

References

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