Reverse overshot water-wheel retroendocytosis of Apo Transferrin extrudes cellular iron.

Sheokand, Navdeep and Malhotra, Himanshu and Chauhan, Anoop Singh and Kumar, Manoj and Chaudhary, Surbhi and Patidar, Anil and Boradia, Vishant Mahendra and Raje, Chaaya Iyengar and Raje, Manoj (2016) Reverse overshot water-wheel retroendocytosis of Apo Transferrin extrudes cellular iron. Journal of cell science, 129. pp. 843-53. ISSN 1477-9137

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Abstract

Iron a vital micronutrient for all organisms must be managed judiciously as both, deficiency or excess can trigger severe pathology. While cellular iron import is well understood its export is thought to be limited to transmembrane extrusion via ferroportin the only known mammalian iron exporter. Utilizing primary cells and cell lines (including those with no discernible expression of ferroportin on their surface) we demonstrate that upon iron loading the multifunctional enzyme Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) that is recruited to the cell surface treadmills apo transferrin (apo Tf) in and out of the cell. Kinetic analysis utilizing; labeled ligand, GAPDH knock down cells, Fe(55) labeled cells and pharmacological inhibitors of endocytosis confirmed GAPDH dependent apo Tf internalization as a prerequisite for cellular iron export. These studies define an unusual rapid recycling process of retroendocytosis for cellular iron 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 iron overload disorders.

Item Type:	Article
Additional Information:	Open Access
Uncontrolled Keywords:	Apotransferrin; GAPDH; Glyceraldehyde-3-phosphate dehydrogenase; Iron; Microscopy; Moonlighting protein; Protein trafficking; Retroendocytosis
Subjects:	Q Science > QR Microbiology
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	29 Sep 2016 06:28
Last Modified:	29 Sep 2016 06:28
URI:	http://crdd.osdd.net/open/id/eprint/1841

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