Expression and role of cubilin in the internalization of nutrients during the peri-implantation development of the rodent embryo

被引:43
作者
Assémat, E
Vinot, S
Gofflot, F
Linsel-Nitschke, P
Illien, F
Châtelet, F
Verroust, P
Louvet-Vallée, S
Rinninger, F
Kozyraki, R
机构
[1] INSERM, UMR 538, F-75012 Paris, France
[2] Univ Paris 06, Fac Med St Antoine, F-75012 Paris, France
[3] Univ Paris 06, Lab Biol Cellulaire Dev, CNRS, UMR7622, F-75012 Paris, France
[4] Catholic Univ Louvain, Unit Dev Genet, B-1200 Brussels, Belgium
[5] Univ Klinikum Hamburg Eppendorf, Dept Internal Med, D-20246 Hamburg, Germany
关键词
cholesterol; cubilin; endocytosis; megalin; peri-implantation development;
D O I
10.1095/biolreprod.104.036913
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Histiotrophic nutrition is essential during the peri-implantation development in rodents, but little is known about receptors involved in protein and lipid endocytosis derived from the endometrium and the uterine glands. Previous studies suggested that cubilin, a multiligand receptor for vitamin, iron, and protein uptake in the adult, might be important in this process, but the onset of its expression and function is not known. In this study, we analyzed the expression of cubilin in the pre- and early post-implantation rodent embryo and tested its potential function in protein and cholesterol uptake. Using morphological and Western blot analysis, we showed that cubilin first appeared at the eight-cell stage. It was expressed by the maternal-fetal interfaces, trophectoderm and visceral endoderm, but also by the future neuroepithelial cells and the developing neural tube. At all these sites, cubilin was localized at the apical pole of the cells exposed to the maternal environment or to the amniotic and neural tube cavities, and had a very similar distribution to megalin, a member of the LDLR gene family and a coreceptor for cubilin in adult tissues. To analyze cubilin function, we followed endocytosis of apolipoprotein A-I and HDL cholesterol, nutrients normally present in the uterine glands and essential for embryonic growth. We showed that internalization of both ligands was cubilin dependent during the early rodent gestation. In conclusion, the early cubilin expression and its function in protein and cholesterol uptake suggest an important role for cubilin in the development of the peri-implantation embryo.
引用
收藏
页码:1079 / 1086
页数:8
相关论文
共 41 条
[1]   Quantitative studies on the mechanisms of amino acid supply to rat embryos during organogenesis [J].
Beckman, DA ;
Lloyd, JB ;
Brent, RL .
REPRODUCTIVE TOXICOLOGY, 1998, 12 (02) :197-200
[2]  
Bielinska M, 1999, INT J DEV BIOL, V43, P183
[3]  
Birn H, 2000, J AM SOC NEPHROL, V11, P191, DOI 10.1681/ASN.V112191
[4]   A two-receptor pathway for catabolism of Clara cell secretory protein in the kidney [J].
Burmeister, R ;
Boe, IM ;
Nykjaer, A ;
Jacobsen, C ;
Moestrup, SK ;
Verroust, P ;
Christensen, EI ;
Lund, J ;
Willnow, TE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (16) :13295-13301
[5]   Uterine glands provide histiotrophic nutrition for the human fetus during the first trimester of pregnancy [J].
Burton, GJ ;
Watson, AL ;
Hempstock, J ;
Skepper, JN ;
Jauniaux, E .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2002, 87 (06) :2954-2959
[6]   Truncated apo B-70.5-containing lipoproteins bind to megalin but not the LDL receptor [J].
Chen, ZJ ;
Saffitz, JE ;
Latour, MA ;
Schonfeld, G .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (10) :1419-1430
[7]   Megalin and cubilin: Multifunctional endocytic receptors [J].
Christensen, EI ;
Birn, H .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2002, 3 (04) :258-268A
[8]  
FLEMING TP, 1986, J EMBRYOL EXP MORPH, V95, P169
[9]   ACTIVATION OF MAMMALIAN OOCYTES BY INTRACELLULAR INJECTION OF CALCIUM [J].
FULTON, BP ;
WHITTINGHAM, DG .
NATURE, 1978, 273 (5658) :149-151
[10]   The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless [J].
Fyfe, JC ;
Madsen, M ;
Hojrup, P ;
Christensen, EI ;
Tanner, SM ;
de la Chapelle, A ;
He, QC ;
Moestrup, SK .
BLOOD, 2004, 103 (05) :1573-1579