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Megalin is a receptor for apolipoprotein M and kidney-specific megalin-deficiency confers urinary excretion of apolipoprotein M.

Faber, Kirsten LU ; Hvidberg, Vibeke ; Moestrup, Søren K ; Dahlbäck, Björn LU and Nielsen, Lars Bo (2006) In Molecular Endocrinology 20(1). p.212-218
Abstract
Apolipoprotein ( apo) M is a novel apolipoprotein belonging to the lipocalin protein superfamily, i.e. proteins binding small lipophilic compounds. Like other apolipoproteins, it is expressed in hepatocytes and secreted into plasma where it associates with high-density lipoprotein particles. In addition, apoM is expressed at high levels in the kidney tubule cells. In this study, we show that the multiligand receptor megalin, which is expressed in kidney proximal tubule cells, is a receptor for apoM and mediates its uptake in the kidney. To examine apoM binding to megalin, a recombinant apoM was expressed in Escherichia coli and used in surface plasmon resonance and cell culture studies. The results showed apoM binding to immobilized... (More)
Apolipoprotein ( apo) M is a novel apolipoprotein belonging to the lipocalin protein superfamily, i.e. proteins binding small lipophilic compounds. Like other apolipoproteins, it is expressed in hepatocytes and secreted into plasma where it associates with high-density lipoprotein particles. In addition, apoM is expressed at high levels in the kidney tubule cells. In this study, we show that the multiligand receptor megalin, which is expressed in kidney proximal tubule cells, is a receptor for apoM and mediates its uptake in the kidney. To examine apoM binding to megalin, a recombinant apoM was expressed in Escherichia coli and used in surface plasmon resonance and cell culture studies. The results showed apoM binding to immobilized megalin [ dissociation constant ( K-d) similar to 0.3-1 mu M] and that the apoM was endocytosed by cultured rat yolk sac cells in a megalin-dependent manner. To examine the importance of apoM binding by megalin in vivo, we analyzed mice with a tissue-specific deficiency of megalin in the kidney. Megalin deficiency was associated with pronounced urinary excretion of apoM, whereas apoM was not detected in normal mouse, human, or rat urine. Gel filtration analysis showed that the urinary apoM-containing particles were small and devoid of apoA-1. The results suggest that apoM binds to megalin and that megalin-mediated endocytosis in kidney proximal tubules prevents apoM excretion in the urine. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Endocrinology
volume
20
issue
1
pages
212 - 218
publisher
The Endocrine Society
external identifiers
  • wos:000234230000017
  • pmid:16099815
  • scopus:29444434760
  • pmid:16099815
ISSN
0888-8809
DOI
10.1210/me.2005-0209
language
English
LU publication?
yes
id
159e2602-9482-4315-a902-0a25d50d35fe (old id 142775)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16099815&dopt=Abstract
date added to LUP
2016-04-01 17:04:25
date last changed
2021-10-10 04:21:17
@article{159e2602-9482-4315-a902-0a25d50d35fe,
  abstract     = {Apolipoprotein ( apo) M is a novel apolipoprotein belonging to the lipocalin protein superfamily, i.e. proteins binding small lipophilic compounds. Like other apolipoproteins, it is expressed in hepatocytes and secreted into plasma where it associates with high-density lipoprotein particles. In addition, apoM is expressed at high levels in the kidney tubule cells. In this study, we show that the multiligand receptor megalin, which is expressed in kidney proximal tubule cells, is a receptor for apoM and mediates its uptake in the kidney. To examine apoM binding to megalin, a recombinant apoM was expressed in Escherichia coli and used in surface plasmon resonance and cell culture studies. The results showed apoM binding to immobilized megalin [ dissociation constant ( K-d) similar to 0.3-1 mu M] and that the apoM was endocytosed by cultured rat yolk sac cells in a megalin-dependent manner. To examine the importance of apoM binding by megalin in vivo, we analyzed mice with a tissue-specific deficiency of megalin in the kidney. Megalin deficiency was associated with pronounced urinary excretion of apoM, whereas apoM was not detected in normal mouse, human, or rat urine. Gel filtration analysis showed that the urinary apoM-containing particles were small and devoid of apoA-1. The results suggest that apoM binds to megalin and that megalin-mediated endocytosis in kidney proximal tubules prevents apoM excretion in the urine.},
  author       = {Faber, Kirsten and Hvidberg, Vibeke and Moestrup, Søren K and Dahlbäck, Björn and Nielsen, Lars Bo},
  issn         = {0888-8809},
  language     = {eng},
  number       = {1},
  pages        = {212--218},
  publisher    = {The Endocrine Society},
  series       = {Molecular Endocrinology},
  title        = {Megalin is a receptor for apolipoprotein M and kidney-specific megalin-deficiency confers urinary excretion of apolipoprotein M.},
  url          = {http://dx.doi.org/10.1210/me.2005-0209},
  doi          = {10.1210/me.2005-0209},
  volume       = {20},
  year         = {2006},
}