Nutrient deprivation alters the rate of COPII subunit recruitment at ER subdomains to tune secretory protein transport

William Kasberg, Peter Luong, Kevin A. Swift and Anjon Audhya ()
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William Kasberg: University of Wisconsin School of Medicine and Public Health
Peter Luong: University of Wisconsin School of Medicine and Public Health
Kevin A. Swift: University of Wisconsin School of Medicine and Public Health
Anjon Audhya: University of Wisconsin School of Medicine and Public Health

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Co-assembly of the multilayered coat protein complex II (COPII) with the Sar1 GTPase at subdomains of the endoplasmic reticulum (ER) enables secretory cargoes to be concentrated efficiently within nascent transport intermediates, which subsequently deliver their contents to ER-Golgi intermediate compartments. Here, we define the spatiotemporal accumulation of native COPII subunits and secretory cargoes at ER subdomains under differing nutrient availability conditions using a combination of CRISPR/Cas9-mediated genome editing and live cell imaging. Our findings demonstrate that the rate of inner COPII coat recruitment serves as a determinant for the pace of cargo export, irrespective of COPII subunit expression levels. Moreover, increasing inner COPII coat recruitment kinetics is sufficient to rescue cargo trafficking deficits caused by acute nutrient limitation. Our findings are consistent with a model in which the rate of inner COPII coat addition acts as an important control point to regulate cargo export from the ER.

Date: 2023
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DOI: 10.1038/s41467-023-44002-7

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