Contribution of cubilin and amnionless to processing and membrane targeting of cubilin-amnionless complex

被引:78
作者
Coudroy, G
Gburek, J
Kozyraki, R
Madsen, M
Trugnan, G
Moestrup, SK
Verroust, PJ
Maurice, M
机构
[1] Ctr Hosp Univ St Antoine, INSERM, U538, F-75012 Paris, France
[2] Univ Paris 06, Paris, France
[3] Univ Wroclaw, Dept Pharmaceut Biochem, PL-50138 Wroclaw, Poland
[4] Univ Aarhus, Dept Med Biochem, Aarhus, Denmark
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2005年 / 16卷 / 08期
关键词
D O I
10.1681/ASN.2004110925
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Cubilin is a peripheral apical membrane receptor for multiple ligands that are taken up in several absorptive epithelia. Recently, amnionless (AMN) was identified to form a functional receptor complex with cubilin. By expression in transfected polarized MDCK cells of AMN and several cubilin fragments, including a functional "mini" version of cubilin, the processing, sorting, and membrane anchoring of the complex to the apical membrane were investigated. The results show that truncation mutants, including the N-terminal domain of cubilin, did not appear at the plasma membrane but instead were retained in the endoplasmic reticulum or partially secreted into the medium. Coexpression with AMN led to efficient transport to the apical cell surface of the cubilin constructs, which included the EGF domains, and prevented release into the medium. AMN co-precipitated with cubilin and co-localized with cubilin at the apical cell surface. Apical sorting was observed for a broad set of nonoverlapping cubilin fragments without the N-terminal region, in the absence of AMN. The preference for apical sorting disappeared when glycosylation was inhibited by tunicamycin. In conclusion, it is shown that both units contribute to the processing of the cubilin-AMN complex to the apical membrane: AMN interacts with the EGF domains of cubilin and is responsible for membrane attachment and export of the complex from the endoplasmic reticulum, whereas the extracellular cubilin molecule is responsible for apical sorting of the complex in a carbohydrate-dependent manner.
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页码:2330 / 2337
页数:8
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