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Reverse overshot water-wheel retroendocytosis of apotransferrin extrudes cellular iron.
Sheokand, Navdeep; Malhotra, Himanshu; Chauhan, Anoop Singh; Kumar, Manoj; Chaudhary, Surbhi; Patidar, Anil; Boradia, Vishant Mahendra; Raje, Chaaya Iyengar; Raje, Manoj.
Afiliación
  • Sheokand N; Institute of Microbial Technology, CSIR, Sector 39A, Chandigarh 160036, India.
  • Malhotra H; Institute of Microbial Technology, CSIR, Sector 39A, Chandigarh 160036, India.
  • Chauhan AS; Institute of Microbial Technology, CSIR, Sector 39A, Chandigarh 160036, India.
  • Kumar M; Institute of Microbial Technology, CSIR, Sector 39A, Chandigarh 160036, India.
  • Chaudhary S; Institute of Microbial Technology, CSIR, Sector 39A, Chandigarh 160036, India.
  • Patidar A; Institute of Microbial Technology, CSIR, Sector 39A, Chandigarh 160036, India.
  • Boradia VM; National Institute of Pharmaceutical Education & Research, Phase X, Sector 67, SAS Nagar, Punjab 160062, India.
  • Raje CI; National Institute of Pharmaceutical Education & Research, Phase X, Sector 67, SAS Nagar, Punjab 160062, India.
  • Raje M; Institute of Microbial Technology, CSIR, Sector 39A, Chandigarh 160036, India manoj@imtech.res.in.
J Cell Sci ; 129(4): 843-53, 2016 Feb 15.
Article en En | MEDLINE | ID: mdl-26743084
ABSTRACT
Iron (Fe), a vital micronutrient for all organisms, must be managed judiciously because both deficiency or excess can trigger severe pathology. Although cellular Fe import is well understood, its export is thought to be limited to transmembrane extrusion through ferroportin (also known as Slc40a1), the only known mammalian Fe exporter. Utilizing primary cells and cell lines (including those with no discernible expression of ferroportin on their surface), we demonstrate that upon Fe loading, the multifunctional enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is recruited to the cell surface, 'treadmills' apotransferrin in and out of the cell. Kinetic analysis utilizing labeled ligand, GAPDH-knockdown cells, (55)Fe-labeled cells and pharmacological inhibitors of endocytosis confirmed GAPDH-dependent apotransferrin internalization as a prerequisite for cellular Fe export. These studies define an unusual rapid recycling process of retroendocytosis for cellular Fe extrusion, a process mirroring receptor mediated internalization that has never before been considered for maintenance of cellular cationic homeostasis. Modulation of this unusual pathway could provide insights for management of Fe overload disorders.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Apoproteínas / Transferrina / Endocitosis / Hierro Límite: Animals Idioma: En Revista: J Cell Sci Año: 2016 Tipo del documento: Article País de afiliación: India

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Apoproteínas / Transferrina / Endocitosis / Hierro Límite: Animals Idioma: En Revista: J Cell Sci Año: 2016 Tipo del documento: Article País de afiliación: India