TY - JOUR
T1 - Cerebellar ataxia disease-associated Snx14 promotes lipid droplet growth at ER-droplet contacts
AU - Datta, Sanchari
AU - Liu, Yang
AU - Hariri, Hanaa
AU - Bowerman, Jade
AU - Henne, W. Mike
N1 - Funding Information:
W.M. Henne, S. Datta, Y. Liu, and H. Hariri are supported by grants from the Welch Foundation (I-1873), the Searle Foundation (SSP-2016-1482), the National Institutes of Health National Institute of General Medical Sciences (GM119768), and the University of Texas Southwestern Endowed Scholars Program. The authors declare no competing financial interests.
Publisher Copyright:
© 2019 Datta et al.
PY - 2019
Y1 - 2019
N2 - Lipid droplets (LDs) are nutrient reservoirs used by cells to maintain homeostasis. Nascent droplets form on the endoplasmic reticulum (ER) and grow following an influx of exogenous fatty acids (FAs). The budding of LDs requires extensive ER-LD crosstalk, but how this is regulated remains poorly understood. Here, we show that sorting nexin protein Snx14, an ERresident protein associated with the cerebellar ataxia SCAR20, localizes to ER-LD contacts following FA treatment, where it promotes LD maturation. Using proximity-based APEX technology and topological dissection, we show that Snx14 accumulates specifically at ER-LD contacts independently of Seipin, where it remains ER-anchored and binds LDs in trans. SNX14KO cells exhibit perturbed LD morphology, whereas Snx14 overexpression promotes LD biogenesis and extends ER-LD contacts. Multi-time point imaging reveals that Snx14 is recruited to ER microdomains containing the fatty acyl-CoA ligase ACSL3, where nascent LDs bud. We propose that Snx14 is a novel marker for ER-LD contacts and regulates FA-stimulated LD growth.
AB - Lipid droplets (LDs) are nutrient reservoirs used by cells to maintain homeostasis. Nascent droplets form on the endoplasmic reticulum (ER) and grow following an influx of exogenous fatty acids (FAs). The budding of LDs requires extensive ER-LD crosstalk, but how this is regulated remains poorly understood. Here, we show that sorting nexin protein Snx14, an ERresident protein associated with the cerebellar ataxia SCAR20, localizes to ER-LD contacts following FA treatment, where it promotes LD maturation. Using proximity-based APEX technology and topological dissection, we show that Snx14 accumulates specifically at ER-LD contacts independently of Seipin, where it remains ER-anchored and binds LDs in trans. SNX14KO cells exhibit perturbed LD morphology, whereas Snx14 overexpression promotes LD biogenesis and extends ER-LD contacts. Multi-time point imaging reveals that Snx14 is recruited to ER microdomains containing the fatty acyl-CoA ligase ACSL3, where nascent LDs bud. We propose that Snx14 is a novel marker for ER-LD contacts and regulates FA-stimulated LD growth.
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U2 - 10.1083/jcb.201808133
DO - 10.1083/jcb.201808133
M3 - Article
C2 - 30765438
AN - SCOPUS:85064191678
SN - 0021-9525
VL - 218
SP - 1335
EP - 1351
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -