tailieunhanh - Báo cáo khoa học: Megalin binds and mediates cellular internalization of folate binding protein

Folate is an essential vitamin involved in a number of biological processes. High affinity folate binding proteins (FBPs) exist both as glycosylphospha-tidylinositol-linked, membrane associated folate binding proteins and as soluble FBPs in plasma and some secretory fluids such as milk, saliva and semen. The function and significance of FBPs are unresolved, however, it has been suggested that they may facilitate folate uptake, . during suck-ling. | ềFEBS Journal Megalin binds and mediates cellular internalization of folate binding protein Henrik Birn1 Xiaoyue Zhai1 Jan Holm2 Steen I. Hansen2 Christian Jacobsen3 Erik I. Christensen1 and S0ren K. Moestrup3 1 Department of Cell Biology Institute of Anatomy University of Aarhus Denmark 2 Department of of ClinicalChemistry Hillerod Hospital Denmark 3 Department of MedicalBiochemistry University of Aarhus Denmark Keywords absorption endocytosis intestine kidney vitamins Correspondence H. Birn Department of CellBiology Institute of Anatomy University of Aarhus University Park Building 234 DK-8000 Aarhus C Denmark Fax 45 86198664 Tel 45 89423051 E-mail hb@ Received 15 March 2005 revised 4 July 2005 accepted 11 July 2005 doi Folate is an essential vitamin involved in a number of biological processes. High affinity folate binding proteins FBPs exist both as glycosylphospha-tidylinositol-linked membrane associated folate binding proteins and as soluble FBPs in plasma and some secretory fluids such as milk saliva and semen. The function and significance of FBPs are unresolved however it has been suggested that they may facilitate folate uptake . during suckling. The present study shows that megalin a large multiligand endocytic receptor and member of the low-density lipoprotein-receptor family is able to bind and mediate cellular uptake of FBP. Surface plasmon resonance analysis shows binding of bovine and human milk FBP to immobilized megalin but not to low density lipoprotein receptor related protein. Binding of 125I-labeled folate binding protein FBP to sections of kidney proximal tubule known to express high levels of megalin is inhibitable by excess unlabeled FBP and by receptor associated protein a known inhibitor of binding to megalin. Immortalized rat yolk sac cells representing an established model for studying megalin-mediated uptake reveal 125I-labeled FBP uptake which is inhibited by receptor associated protein and