The Drosophila orthologs of cubilin and amnionless are specifically expressed in nephrocytes, which function in both filtration and protein reabsorption. The role of the cubilin/amnionless receptor complex in flies appears to be analogous to that of human cubilin/amnionless receptor complex in the proximal tubules of the kidney [reviewed in FBrf0220711 and FBrf0235870; see also the human disease model report 'kidney disease (fly models overview)' FBhh0000738]. The human gene that encodes amnionless is AMN; there is a single orthologous gene in Drosophila, Amnionless, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated. See also the disease model reports for 'kidney disease (postulated), CUBN-related' (FBhh0000550) and 'megaloblastic anemia 1' (MGA1, FBhh0000082).
A UAS construct of the human Hsap\AMN has been introduced into flies. Heterologous rescue (functional complementation) is observed: overexpression of the human gene rescues a protein-marker-uptake phenotype observed for Amnionless knockdown effected by RNAi.
The expression of Dmel\Amnionless is restricted to the fly nephrocytes. Using a driver specific for expression in pericardial nephrocytes, RNAi-effected knockdown of Amnionless blocks uptake of a protein marker into the nephrocyte and results in impaired nephrocyte endocytic function. Knockdown of Amnionless does not cause significant changes in viability under normal conditions, however, under conditions of toxin stress viability is significantly reduced.
[updated Jun. 2017 by FlyBase; FBrf0222196]
The cubilin/amnionless receptor complex in human is expressed in both the small intestine and the proximal tubules of the kidney. In the proximal tubules, cubilin is involved in the reabsorption of several filtered plasma proteins, including vitamin carriers and lipoproteins. Consistent with this, low-molecular-weight proteinuria is often observed in patients with megaloblastic anemia 1. (Storm et al., 2013; pubmed:24156255)
One to one: 1 human to 1 Drosophila.
Moderate-scoring ortholog of human AMN (reciprocal best hit; 1 Drosophila to 1 human). Dmel\Amnionless shares 21% identity and 32% similarity with the human gene.
