Reticulon 3 Regulates Very Low Density Lipoprotein Secretion By Controlling Very Low Density Lipoprotein Transport Vesicle Biogenesis

Keywords

Apolipoprotein B; Coat complex II; Endoplasmic reticulum; Reticulon 3; Triacylglycerol; Very low density lipoprotein; VLDL transport vesicle

Abstract

Secretion of very low density lipoprotein (VLDL) by the liver is an important physiological process; however, the rate of VLDL secretion is determined by its transport from the endoplasmic reticulum (ER) to the Golgi. This transport event is facilitated by a specialized ER-derived vesicle, the VLDL transport vesicle (VTV). We have reported earlier a detailed VTV proteome, which revealed that reticulon 3 (RTN3) is uniquely present in the VTV. Our immunoblotting and electron microscopic data demonstrate that RTN3 is enriched in the VTV; however, other ER-derived vesicles do not contain RTN3. Coimmunoprecipitation data coupled with confocal microscopic analyses strongly suggest that RTN3 interacts with VLDL core protein, apoB100, at the ER level. Our data show that either blocking of RTN3 using specific antibodies or RTN3 knockdown resulted in significant reduction in VTV biogenesis from hepatic ER membranes. Additionally, VLDL secretion from hepatocytes was significantly decreased when RTN3 was silenced by RTN3 siRNA. We conclude that RTN3 regulates VLDL secretion by controlling VTV-mediated ER-to-Golgi transport of nascent VLDL.

Publication Date

1-1-2018

Publication Title

Canadian Journal of Physiology and Pharmacology

Volume

96

Issue

7

Number of Pages

668-675

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1139/cjpp-2018-0077

Socpus ID

85049865508 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/85049865508

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