Functional study of mammalian Neph proteins in Drosophila melanogaster.
Neph molecules are highly conserved immunoglobulin superfamily proteins (IgSF) which are essential for multiple morphogenetic processes, including glomerular development in mammals and neuronal as well as nephrocyte development in D. melanogaster. While D. melanogaster expresses two Neph-like proteins (Kirre and IrreC/Rst), three Neph proteins (Neph1-3) are expressed in the mammalian system. However, although these molecules are highly abundant, their molecular functions are still poorly understood. Here we report on a fly system in which we overexpress and replace endogenous Neph homologs with mammalian Neph1-3 proteins to identify functional Neph protein networks required for neuronal and nephrocyte development. Misexpression of Neph1, but neither Neph2 nor Neph3, phenocopies the overexpression of endogenous Neph molecules suggesting a functional diversity of mammalian Neph family proteins. Moreover, structure-function analysis identified a conserved and specific Neph1 protein motif that appears to be required for the functional replacement of Kirre. Hereby, we establish D. melanogaster as a genetic system to specifically model molecular Neph1 functions in vivo and identify a conserved amino acid motif linking Neph1 to Drosophila Kirre function.
Renal Division, University Hospital Freiburg, Freiburg, Germany.
Martin
M
Helmstädter
Kevin
K
Lüthy
Markus
M
Gödel
Matias
M
Simons
Ashish
Deepak
D
Nihalani
Stefan A
SA
Rensing
Karl-Friedrich
KF
Fischbach
Tobias B
TB
Huber
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D002459:Cell Fusion; D016384:Consensus Sequence; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression; D007136:Immunoglobulins / Q000096:biosynthesis / Q000235:genetics*; D007814:Larva / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D051379:Mice; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D010641:Phenotype; D010802:Phylogeny; D019076:Transgenes
D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D005136:Eye Proteins; D007136:Immunoglobulins; C486606:Kirrel1 protein, mouse; C474214:Kirrel3 protein, mouse; D008565:Membrane Proteins; D009124:Muscle Proteins; C546601:Neph3 protein, mouse; C413082:kirre protein, Drosophila; C085209:rst protein, Drosophila