Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/103125
Title: Sec24D-dependent transport of extracellular matrix proteins is required for zebrafish skeletal morphogenesis
Author: Sarmah, Swapnalee
Barrallo-Gimeno, Alejandro
Melville, David B.
Topczewski, Jacek
Solnica-Krezel, Liliana
Knapik, Ela W.
Keywords: Proteïnes de membrana
Proteïnes portadores
Matriu extracel·lular
Peix zebra
Esquelet
Morfogènesi
Membrane proteins
Carrier proteins
Extracellular matrix
Zebra danio
Skeleton
Morphogenesis
Issue Date: 28-Apr-2010
Publisher: Public Library of Science (PLoS)
Abstract: Protein transport from endoplasmic reticulum (ER) to Golgi is primarily conducted by coated vesicular carriers such as COPII. Here, we describe zebrafish bulldog mutations that disrupt the function of the cargo adaptor Sec24D, an integral component of the COPII complex. We show that Sec24D is essential for secretion of cartilage matrix proteins, whereas the preceding development of craniofacial primordia and pre-chondrogenic condensations does not depend on this isoform. Bulldog chondrocytes fail to secrete type II collagen and matrilin to extracellular matrix (ECM), but membrane bound receptor β1-Integrin and Cadherins appear to leave ER in Sec24D-independent fashion. Consequently, Sec24D-deficient cells accumulate proteins in the distended ER, although a subset of ER compartments and Golgi complexes as visualized by electron microscopy and NBD C6-ceramide staining appear functional. Consistent with the backlog of proteins in the ER, chondrocytes activate the ER stress response machinery and significantly upregulate BiP transcription. Failure of ECM secretion hinders chondroblast intercalations thus resulting in small and malformed cartilages and severe craniofacial dysmorphology. This defect is specific to Sec24D mutants since knockdown of Sec24C, a close paralog of Sec24D, does not result in craniofacial cartilage dysmorphology. However, craniofacial development in double Sec24C/Sec24D-deficient animals is arrested earlier than in bulldog/sec24d, suggesting that Sec24C can compensate for loss of Sec24D at initial stages of chondrogenesis, but Sec24D is indispensable for chondrocyte maturation. Our study presents the first developmental perspective on Sec24D function and establishes Sec24D as a strong candidate for cartilage maintenance diseases and craniofacial birth defects.
Note: Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0010367
It is part of: PLoS One, 2010, vol. 5, num. 4, p. e10367
Related resource: https://doi.org/10.1371/journal.pone.0010367
URI: http://hdl.handle.net/2445/103125
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

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