Molekulargenetisches Labor
Zentrum für Nephrologie und Stoffwechsel
Moldiag Erkrankungen Gene Support Kontakt

Endozytosestörungen der proximalen Tubulusfunktion

In der Gruppe proximal tubulärer Erkrankungen, die auf einer Endozytosestörung beruhen, werden die verschiedenen Protein-Rezeptor-Defekte zusammengefasst. Im wesentlichen präsentieren sich diese Störungen auch als Fanconi-Syndrom, jedoch überwiegt sehr stark die tubuläre Proteinurie. Auch der Mangel an proteingebundenen fettlöslichen Hormonen und Vitaminen kann klinisch in Erscheinung treten.

Differentialdiagnostische Abgrenzung

Die Gruppe der Endozytosestörungen und die Gruppe der metabolischen Störungen sind recht überlappend. Zum einen ist die Endozytose ein Energiekonsumierender Prozess, so dass Störungen des Energiestoffwechsels auch Störungen der Endozytosefunktion nach sich ziehen müssen. Andererseits führt eine gestörte Endozytose, zum Beispiel durch den fehlerhaften Abbau der aufgenommenen Substanzen zu einer Anreicherung nicht katabolisierbarer Metaboliten letztlich auch zu einer metabolischen Störung der Zellfunktion.

Symptome

Proximaler Tubulusschaden
Bei Endozytosestörungen des proximalen Tubulus ist das Fanconis Syndrom vor allem durch die massive tubuläre Proteinurie dominiert.

Gliederung

Genetisch bedingte Störungen der proximalen Tubulusfunktion
Endozytosestörungen der proximalen Tubulusfunktion
Donnai-Barrow-Syndrom
LRP2
Imerslund-Grasbeck-Syndrom
AMN
CUBN
Fanconi-Syndrom
Metabolische Störungen der proximalen Tubulusfunktion
Spezifische Transportstörungen des proximalen Tubulus

Referenzen:

1.

Birn H et al. (1997) Characterization of an epithelial approximately 460-kDa protein that facilitates endocytosis of intrinsic factor-vitamin B12 and binds receptor-associated protein.

external link
2.

de Ligt J et al. (2012) Diagnostic exome sequencing in persons with severe intellectual disability.

external link
3.

Tramontano A et al. (2004) Conformation and glycosylation of a megalin fragment correlate with nephritogenicity in Heymann nephritis.

external link
4.

Hammes A et al. (2005) Role of endocytosis in cellular uptake of sex steroids.

external link
5.

Naccache SN et al. (2006) Binding of internalized receptors to the PDZ domain of GIPC/synectin recruits myosin VI to endocytic vesicles.

external link
6.

Caruso-Neves C et al. (2006) PKB and megalin determine the survival or death of renal proximal tubule cells.

external link
7.

Kantarci S et al. (2007) Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes.

external link
8.

Fyfe JC et al. (1991) Inherited selective intestinal cobalamin malabsorption and cobalamin deficiency in dogs.

external link
9.

Aminoff M et al. (1995) Selective intestinal malabsorption of vitamin B12 displays recessive mendelian inheritance: assignment of a locus to chromosome 10 by linkage.

external link
10.

Bork P et al. (1993) The CUB domain. A widespread module in developmentally regulated proteins.

external link
11.

Seetharam B et al. (1997) Identification of rat yolk sac target protein of teratogenic antibodies, gp280, as intrinsic factor-cobalamin receptor.

external link
12.

Nagai M et al. (2003) The adaptor protein ARH escorts megalin to and through endosomes.

external link
13.

Moestrup SK et al. (1998) The intrinsic factor-vitamin B12 receptor and target of teratogenic antibodies is a megalin-binding peripheral membrane protein with homology to developmental proteins.

external link
14.

Kozyraki R et al. (1998) The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region.

external link
15.

Aminoff M et al. (1999) Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1.

external link
16.

Kozyraki R et al. (1999) The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein.

external link
17.

Xu D et al. (1999) Genetic evidence of an accessory activity required specifically for cubilin brush-border expression and intrinsic factor-cobalamin absorption.

external link
18.

Kristiansen M et al. (2000) Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin.

external link
19.

Fyfe JC et al. (2004) The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless.

external link
20.

Andersen CB et al. (2010) Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes.

external link
21.

Storm T et al. (2011) A patient with cubilin deficiency.

external link
22.

Donnai D et al. (1993) Diaphragmatic hernia, exomphalos, absent corpus callosum, hypertelorism, myopia, and sensorineural deafness: a newly recognized autosomal recessive disorder?

external link
23.

Raychowdhury R et al. (1989) Autoimmune target in Heymann nephritis is a glycoprotein with homology to the LDL receptor.

external link
24.

Chatelet F et al. (1986) Ultrastructural localization by monoclonal antibodies of brush border antigens expressed by glomeruli. II. Extrarenal distribution.

external link
25.

Kerjaschki D et al. (1983) Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis rats.

external link
26.

Moestrup SK et al. (1995) Evidence that epithelial glycoprotein 330/megalin mediates uptake of polybasic drugs.

external link
27.

Farquhar MG et al. (1995) The Heymann nephritis antigenic complex: megalin (gp330) and RAP.

external link
28.

Chowdhary BP et al. (1995) In situ hybridization mapping of a 500-kDa calcium-sensing protein gene (LRP2) to human chromosome region 2q31>q32.1 and porcine chromosome region 15q22>q24.

external link
29.

None (1995) The unfolding story of megalin (gp330): now recognized as a drug receptor.

external link
30.

Kounnas MZ et al. (1995) Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin.

external link
31.

Saito A et al. (1994) Complete cloning and sequencing of rat gp330/"megalin," a distinctive member of the low density lipoprotein receptor gene family.

external link
32.

Korenberg JR et al. (1994) Chromosomal localization of human genes for the LDL receptor family member glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1).

external link
33.

Chassaing N et al. (2003) Donnai-Barrow syndrome: four additional patients.

external link
34.

Hjälm G et al. (1996) Cloning and sequencing of human gp330, a Ca(2+)-binding receptor with potential intracellular signaling properties.

external link
35.

Willnow TE et al. (1996) Defective forebrain development in mice lacking gp330/megalin.

external link
36.

Devriendt K et al. (1998) Proteinuria in a patient with the diaphragmatic hernia-hypertelorism-myopia-deafness syndrome: further evidence that the facio-oculo-acoustico-renal syndrome represents the same entity.

external link
37.

Nykjaer A et al. (1999) An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3.

external link
38.

Marinò M et al. (1999) Serum antibodies against megalin (GP330) in patients with autoimmune thyroiditis.

external link
39.

Leheste JR et al. (1999) Megalin knockout mice as an animal model of low molecular weight proteinuria.

external link
40.

Schmitz C et al. (2002) Megalin deficiency offers protection from renal aminoglycoside accumulation.

external link
41.

Nykjaer A et al. (2001) Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3).

external link
42.

OMIM.ORG article

Omim 600073 external link
Update: 14. August 2020
Copyright © 2005-2020 Zentrum für Nephrologie und Stoffwechsel, Dr. Mato Nagel
Albert-Schweitzer-Ring 32, D-02943 Weißwasser, Deutschland, Tel.: +49-3576-287922, Fax: +49-3576-287944
Seitenüberblick | Webmail | Haftungsausschluss | Datenschutz