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First published online 19 August 2008
doi: 10.1242/jcs.031070

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Efficient coupling of Sec23-Sec24 to Sec13-Sec31 drives COPII-dependent collagen secretion and is essential for normal craniofacial development

¹ Cell Biology Laboratories, Department of Biochemistry, University of Bristol School of Medical Sciences, University Walk, Bristol BS8 1TD, UK
² Department of Physiology and Pharmacology, and Wolfson Bioimaging Facility, University of Bristol School of Medical Sciences, University Walk, Bristol BS8 1TD, UK
³ School of Biological Sciences, University of Bristol, Woodland Road, Bristol BS8 1UG, UK

^* Author for correspondence (e-mail: david.stephens{at}bristol.ac.uk)

Accepted 25 June 2008

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.

Key words: COPII, Membrane traffic, Secretion, Vesicle formation

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