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UID:960@biotech.technion.ac.il
DTSTART;TZID=Asia/Jerusalem:20200916T170000
DTEND;TZID=Asia/Jerusalem:20220202T164952
DTSTAMP:20220512T124720Z
URL:https://biotech.technion.ac.il/events/deciphering-the-mechanisms-contr
 olling-mammalian-ferritin-secretion-2/
SUMMARY:Deciphering the Mechanisms Controlling Mammalian Ferritin Secretion
DESCRIPTION:The protein ferritin consists of two kinds of subunits\, H and 
 L\, that assemble to a 24-subunit heteropolymer complex that can store up 
 to 4500 iron atoms. Mammalian ferritin is an actively secreted protein eve
 n though it lacks a signal peptide sequence for classical ER-Golgi secreti
 on. However\, little is known about the mechanisms underlying ferritin sec
 retion and reuptake in mammals. This research focused on deciphering the m
 echanisms controlling ferritin secretion and its regulation. We used cell 
 line models of wild-type and knockout HeLa cells for both ferritin subunit
 s (HeLaFtKO cells) and transfected them with different ferritin constructs
 . We investigated the role of a 13 amino-acid long motif in ferritin secre
 tion. This motif was identified on both ferritin subunits\, which lack the
  classical signal peptide sequence. Additionally\, we examined the role of
  iron in intracellular distribution and secretion of ferritin. Our prelimi
 nary results showed that the ferritin motif led to enhance ferritin secret
 ion. However\, as the research on the ferritin motif continued\, we realiz
 ed that the mutations on the ferritin motif inhibit its internalization vi
 a TfR1. Hence\, the elevation of motif-mutated ferritin in the medium was 
 due to impaired ferritin uptake rather than increased secretion. When we c
 ompared the secretion of mutated and wild-type ferritin\, while blocking t
 he reabsorption of the wild-type ferritin via TfR1\, we saw that the H-sub
 unit motif does not play a role in the regulated secretion of ferritin. In
  contrast\, our results show that the ferritin-iron core is an important f
 actor in the regulation of ferritin secretion\, whereas the cytosolic iron
  levels do not affect the secretion of ferritin. Our results also demonstr
 ate that the secretion and uptake of cellular ferritin is an active cycle\
 , regulated by iron at the level of secretion and the level of uptake. In 
 summary\, these results enhance our understanding on the mechanism control
 ling ferritin secretion\, which is an important piece in the puzzle of tis
 sue iron homeostasis.\n\n \n\nAbstract
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