A molecular switch orchestrates enzyme specificity and secretory granule morphology

Nature Communications
Suena JiKelly G Ten Hagen

Abstract

Regulated secretion is an essential process where molecules destined for export are directed to membranous secretory granules, where they undergo packaging and maturation. Here, we identify a gene (pgant9) that influences the structure and shape of secretory granules within the Drosophila salivary gland. Loss of pgant9, which encodes an O-glycosyltransferase, results in secretory granules with an irregular, shard-like morphology, and altered glycosylation of cargo. Interestingly, pgant9 undergoes a splicing event that acts as a molecular switch to alter the charge of a loop controlling access to the active site of the enzyme. The splice variant with the negatively charged loop glycosylates the positively charged secretory cargo and rescues secretory granule morphology. Our study highlights a mechanism for dictating substrate specificity within the O-glycosyltransferase enzyme family. Moreover, our in vitro and in vivo studies suggest that the glycosylation status of secretory cargo influences the morphology of maturing secretory granules.

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Citations

May 24, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wangsa Tirta IsmayaHeni Rachmawati
Sep 25, 2019·Proceedings of the National Academy of Sciences of the United States of America·Amy J FernandezNadine L Samara
Nov 20, 2019·Proceedings of the National Academy of Sciences of the United States of America·E TianKelly G Ten Hagen
Apr 3, 2019·Glycoconjugate Journal·Weidong LiGuy Smagghe
Nov 28, 2019·Glycoconjugate Journal·Shoko Nishihara
Nov 7, 2019·The Journal of Biological Chemistry·Hayley M ReynoldsKelly G Ten Hagen
Apr 24, 2020·Molecular Cell·Benjamin SchumannCarolyn Ruth Bertozzi
Apr 19, 2021·Advances in Biological Regulation·Cheng-I Jonathan MaJulie A Brill
Jul 21, 2021·Cell Chemical Biology·Daisuke FujinamiWilfred A van der Donk
May 2, 2020·Journal of Chemical Information and Modeling·Benedetta RighinoMaria Cristina De Rosa
Nov 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Liping ZhangKelly G Ten Hagen
Nov 3, 2021·Chembiochem : a European Journal of Chemical Biology·Emili CidFumiichiro Yamamoto

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Datasets Mentioned

BETA
GM130
PXD010548
PDX010549

Methods Mentioned

BETA
glycosylation
transfections
X-ray
electron microscopy
PCR
transgenic
dissection
Infrared Imaging
transfection
electrophoresis

Software Mentioned

NIS
AutoDetect Binary
PyMOL Molecular Graphics System
PHENIX
Binary
PTTTE
Beacon Designer
Autodetect
Nikon
HKL2000

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