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Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure.

Authors:
Merte J, Jensen D, Wright K, Sarsfield S, Wang Y, Schekman R, Ginty DD
Affiliation:
Journal:
Nature cell biology

Abstract

Craniorachischisis is a rare but severe birth defect that results in a completely open neural tube. Mouse mutants in planar cell polarity (PCP) signalling components have deficits in the morphological movements of convergent extension that result in craniorachischisis. Using a forward genetic screen in mice, we identified Sec24b, a cargo-sorting member of the core complex of the endoplasmic reticulum (ER)-to-Golgi transport vesicle COPII, as critical for neural tube closure. Sec24bY613 mutant mice exhibit craniorachischisis, deficiencies in convergent extension and other PCP-related phenotypes. Vangl2, a key component of the PCP-signalling pathway critical for convergent extension, is selectively sorted into COPII vesicles by Sec24b. Moreover, Sec24bY613 genetically interacts with a loss-of-function Vangl2 allele (Vangl2LP), causing a marked increase in the prevalence of spina bifida. Interestingly, the Vangl2 looptail point mutants Vangl2D255E and Vangl2S464N, known to cause defects in convergent extension, fail to sort into COPII vesicles and are trapped in the ER. Thus, during COPII vesicle formation, Sec24b shows cargo specificity for a core PCP component, Vangl2, of which proper ER-to-Golgi transport is essential for the establishment of PCP, convergent extension and closure of the neural tube.

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