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Electron Tomography Revels that Milk Lipids Originate from Endoplasmic Reticulum Domains with Novel Structural Features.
Ladinsky, Mark S; Mardones, Gonzalo A; Orlicky, David J; Howell, Kathryn E; McManaman, James L.
Afiliação
  • Ladinsky MS; Boulder Laboratory for 3D Electron Microscopy of Cells, University of Colorado, Boulder, CO, 80309, USA.
  • Mardones GA; Division of Biology, California Institute of Technology, Pasadena, CA, USA.
  • Orlicky DJ; Department of Cell & Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
  • Howell KE; Instituto de Fisiologia, Universidad Austral de Chile, Valdiva, Chile.
  • McManaman JL; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
J Mammary Gland Biol Neoplasia ; 24(4): 293-304, 2019 12.
Article em En | MEDLINE | ID: mdl-31709487
Lipid droplets (LD) are dynamically-regulated organelles that originate from the endoplasmic reticulum (ER), and function in the storage, trafficking and metabolism of neutral lipids. In mammary epithelial cells (MEC) of lactating animals, intact LD are secreted intact into milk to form milk lipids by a novel apocrine mechanism. The secretion of intact LD and the relatively large amounts of lipid secreted by lactating MEC increase demands on the cellular processes responsible for lipid synthesis and LD formation. As yet these processes are poorly defined due to limited understanding of LD-ER interactions. To overcome these limitations, we used rapid-freezing and freeze-substitution methods in conjunction with 3D electron tomography and high resolution immunolocalization to define interactions between LD with ER in MEC of pregnant and lactating rats. Using these approaches, we identified distinct ER domains that contribute to lipid droplet formation and stabilization and which possess unique features previously unrecognized or not fully appreciated. Our results show nascent lipid droplets within the ER lumen and the association of both forming and mature droplets with structurally unique regions of ER cisternae, characterized by the presence of perilipin-2, a protein implicated in lipid droplet formation, and enzymes involved in lipid synthesis. These data demonstrate that milk lipids originate from LD-ER domains with novel structural features and suggest a mechanism for initial droplet formation in the ER lumen and subsequent maturation of the droplets in association with ER cisternae.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leite / Retículo Endoplasmático / Tomografia com Microscopia Eletrônica / Gotículas Lipídicas / Lipídeos / Glândulas Mamárias Animais Limite: Animals / Pregnancy Idioma: En Revista: J Mammary Gland Biol Neoplasia Assunto da revista: NEOPLASIAS Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leite / Retículo Endoplasmático / Tomografia com Microscopia Eletrônica / Gotículas Lipídicas / Lipídeos / Glândulas Mamárias Animais Limite: Animals / Pregnancy Idioma: En Revista: J Mammary Gland Biol Neoplasia Assunto da revista: NEOPLASIAS Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos