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

Journal of Cell Science
Anna K TownleyDavid J Stephens

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 (Sec23/2...Continue Reading

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Citations

Feb 24, 2012·Nature·Lingyan JinMichael Rape
Dec 24, 2011·Nature Cell Biology·Giulia ZanettiRandy Schekman
Sep 4, 2013·Nature Cell Biology·Jeanne C StachowiakElizabeth A Miller
Jun 6, 2012·The Journal of Biological Chemistry·Dustin C BagleyDiane M Ward
Apr 24, 2009·Molecular Biology of the Cell·Krysten J PalmerDavid J Stephens
Apr 29, 2011·Molecular Biology of the Cell·Kota SaitoToshiaki Katada
Jun 28, 2011·Journal of Experimental Botany·Renata CongerFederica Brandizzi
Sep 29, 2012·Science·Rossella VendittiMaria Antonietta De Matteis
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Mar 23, 2013·Biology Open·Katy SchmidtDavid J Stephens
Jul 30, 2009·Journal of Cell Science·Helen HughesDavid J Stephens
Feb 15, 2012·Journal of Cell Science·Anna K TownleyDavid J Stephens
Mar 17, 2012·Journal of Cell Science·Timothy Jarvela, Adam D Linstedt
Jun 5, 2010·PLoS Genetics·Elke GrönnigerFrank Lyko
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