A Caltech Library Service

Perilipin-2 promotes lipid droplet-plasma membrane interactions that facilitate apocrine lipid secretion in secretory epithelial cells of the mouse mammary gland

Monks, Jenifer and Orlicky, David J. and Libby, Andrew E. and Dzieciatkowska, Monica and Ladinsky, Mark S. and McManaman, James L. (2022) Perilipin-2 promotes lipid droplet-plasma membrane interactions that facilitate apocrine lipid secretion in secretory epithelial cells of the mouse mammary gland. Frontiers in Cell and Developmental Biology, 10 . Art. No. 958566. ISSN 2296-634X. PMCID PMC9500548. doi:10.3389/fcell.2022.958566.

Full text is not posted in this repository. Consult Related URLs below.

Use this Persistent URL to link to this item:


Secretory epithelial cells (sMEC) in mammary glands of lactating animals secrete lipids by a novel apocrine mechanism in which cytoplasmic lipid droplets (LD) contact and are enveloped by elements of the apical plasma membrane (APM) before being released into the lumen of the gland as membrane bound structures. The molecular properties of LD-APM contacts and the mechanisms regulating LD membrane envelopment and secretion are not fully understood. Perilipin-2 (Plin2) is a constitutive LD protein that has been proposed to tether LD to the APM through formation of a complex with the transmembrane protein, butyrophilin1a1 (BTN) and the redox enzyme, xanthine oxidoreductase (XOR). Using mice lacking Plin2 and physiological inhibition of apocrine lipid secretion, we demonstrate that LD-APM contact and envelopment are mechanistically distinct steps that they are differentially regulated by Plin2 and independent of LD secretion. We find that Plin2 is not required for formation of LD-APM contacts. However, it increases the percentage of LD that contact the APM and mediates enlargement of the LD-APM contact zone as LD undergo membrane envelopment. The effects of Plin2 LD-APM interactions are associated with increased abundances of BTN, XOR and Cidea, which are implicated as mediators of LD-APM contact formation, on membranes surrounding secreted LD, and with promotion of glycocalyx remodeling at LD-APM contact sites. We propose that Plin2 does not directly mediate contact between LD and the APM but acts by enhancing molecular interactions that stabilize LD-APM contacts and govern membrane envelopment of LD during apocrine lipid secretion. Plin2 does not appear to significantly affect the lipid content of milk in fully lactating animals, but it does increase lipid secretion at the onset of lactation in primaparous dams, which suggest a role in facilitating apocrine lipid secretion in sMEC during their initial transition to a secretory phenotype.

Item Type:Article
Related URLs:
URLURL TypeDescription spectrometry proteomics dataset material CentralArticle
Monks, Jenifer0000-0002-7990-3389
Orlicky, David J.0000-0002-0417-1400
Libby, Andrew E.0000-0003-3726-2170
Dzieciatkowska, Monica0000-0002-9947-2520
Ladinsky, Mark S.0000-0002-1036-3513
McManaman, James L.0000-0003-4735-6429
Additional Information:This work was supported by NIH 2R01HD45965 (JLM) and R01HD093729 (JLM and JM). The authors thank E. Erin Smith, Allison Quador and Jessica Arnold in the University of Colorado Histology Shared Resource Facility, and the technical assistance of the Proteomics Core Facility, which are supported by the University of Colorado Cancer Center Grant (P30CA046934), for help with tissue processing and immunohistochemical studies and proteomics analyses respectively. Imaging experiments were performed in the Advanced Light Microscopy Core Facility of the NeuroTechnology Center at University of Colorado Anschutz Medical Campus, which is supported in part by Rocky Mountain Neurological Disorders Core Grant (P30 NS048154) and by Diabetes Research Center Grant (P30 DK116073).
Funding AgencyGrant Number
PubMed Central ID:PMC9500548
Record Number:CaltechAUTHORS:20221005-265369100.11
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:117273
Deposited By: Melissa Ray
Deposited On:12 Oct 2022 19:59
Last Modified:12 Oct 2022 22:15

Repository Staff Only: item control page