Functional study of mammalian Neph proteins in Drosophila melanogaster
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Functional study of mammalian Neph proteins in Drosophila melanogaster. / Helmstädter, Martin; Lüthy, Kevin; Gödel, Markus; Simons, Matias; Ashish; Nihalani, Deepak; Rensing, Stefan A; Fischbach, Karl-Friedrich; Huber, Tobias B.
In: PLOS ONE, Vol. 7, No. 7, 2012, p. e40300.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Functional study of mammalian Neph proteins in Drosophila melanogaster
AU - Helmstädter, Martin
AU - Lüthy, Kevin
AU - Gödel, Markus
AU - Simons, Matias
AU - Ashish, null
AU - Nihalani, Deepak
AU - Rensing, Stefan A
AU - Fischbach, Karl-Friedrich
AU - Huber, Tobias B
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Amino Acid Motifs
KW - Amino Acid Sequence
KW - Animals
KW - Cell Adhesion Molecules, Neuronal
KW - Cell Fusion
KW - Consensus Sequence
KW - Drosophila Proteins
KW - Drosophila melanogaster
KW - Evolution, Molecular
KW - Eye Proteins
KW - Gene Expression
KW - Immunoglobulins
KW - Larva
KW - Membrane Proteins
KW - Mice
KW - Muscle Proteins
KW - Phenotype
KW - Phylogeny
KW - Transgenes
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1371/journal.pone.0040300
DO - 10.1371/journal.pone.0040300
M3 - SCORING: Journal article
C2 - 22792268
VL - 7
SP - e40300
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 7
ER -
