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A model organism approach

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A model organism approach : defining the role of Neph proteins as regulators of neuron and kidney morphogenesis. / Neumann-Haefelin, Elke; Kramer-Zucker, Albrecht; Slanchev, Krasimir; Hartleben, Björn; Noutsou, Foteini; Martin, Katrin; Wanner, Nicola; Ritter, Alexander; Gödel, Markus; Pagel, Philip; Fu, Xiao; Müller, Alexandra; Baumeister, Ralf; Walz, Gerd; Huber, Tobias B.

in: HUM MOL GENET, Jahrgang 19, Nr. 12, 15.06.2010, S. 2347-59.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Neumann-Haefelin, E, Kramer-Zucker, A, Slanchev, K, Hartleben, B, Noutsou, F, Martin, K, Wanner, N, Ritter, A, Gödel, M, Pagel, P, Fu, X, Müller, A, Baumeister, R, Walz, G & Huber, TB 2010, 'A model organism approach: defining the role of Neph proteins as regulators of neuron and kidney morphogenesis', HUM MOL GENET, Jg. 19, Nr. 12, S. 2347-59. https://doi.org/10.1093/hmg/ddq108

APA

Neumann-Haefelin, E., Kramer-Zucker, A., Slanchev, K., Hartleben, B., Noutsou, F., Martin, K., Wanner, N., Ritter, A., Gödel, M., Pagel, P., Fu, X., Müller, A., Baumeister, R., Walz, G., & Huber, T. B. (2010). A model organism approach: defining the role of Neph proteins as regulators of neuron and kidney morphogenesis. HUM MOL GENET, 19(12), 2347-59. https://doi.org/10.1093/hmg/ddq108

Vancouver

Neumann-Haefelin E, Kramer-Zucker A, Slanchev K, Hartleben B, Noutsou F, Martin K et al. A model organism approach: defining the role of Neph proteins as regulators of neuron and kidney morphogenesis. HUM MOL GENET. 2010 Jun 15;19(12):2347-59. https://doi.org/10.1093/hmg/ddq108

Bibtex

@article{c8bfd534b48f459ea3712394fe2e2929,
title = "A model organism approach: defining the role of Neph proteins as regulators of neuron and kidney morphogenesis",
abstract = "Mutations of the immunoglobulin superfamily proteins nephrin and Neph1 lead to congenital nephrotic syndrome in humans or mice. Neph proteins are three closely related molecules that are evolutionarily conserved and mediate cell recognition. Their importance for morphogenetic processes including the formation of the kidney filtration barrier in vertebrates and synaptogenesis in Caenorhabditis elegans has recently been uncovered. However, the individual morphogenetic function of mammalian Neph1-3 isoforms remained elusive. We demonstrate now that the Neph/nephrin family proteins can form cell-cell adhesion modules across species. Expression of all three mammalian Neph isoforms partially rescued mutant C. elegans lacking their Neph homolog syg-1 and restored synapse formation, suggesting a functional redundancy between the three isoforms. Strikingly, the rescue of defective synaptic connectivity was prevented by deletion of the highly conserved cytoplasmic PSD95/Dlg/ZO-1-binding motif of SYG-1/Neph proteins, indicating the critical role of this intracellular signaling motif for SYG-1/Neph-dependent morphogenetic events. To determine the significance of Neph isoform redundancy for vertebrate kidney development, we analyzed the expression pattern and the functional role of Neph proteins in zebrafish. In situ hybridizations identified zNeph1 and zNeph2 as glomerular proteins. Morpholino knockdown of either zNeph1 or zNeph2 resulted in loss of slit diaphragms and leakiness of the glomerular filtration barrier. This is the first report utilizing C. elegans to study mammalian Neph/nephrin protein function and to demonstrate a functional overlap of Neph1-3 proteins. Furthermore, we identify Neph2 as a novel critical regulator of glomerular function, indicating that both Neph1 and Neph2 are required for glomerular maintenance and development.",
keywords = "Amino Acid Sequence, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cell Adhesion, HeLa Cells, Humans, Immunoglobulins, Kidney, Membrane Proteins, Mice, Models, Animal, Morphogenesis, Neurons, PDZ Domains, Phylogeny, Journal Article, Research Support, Non-U.S. Gov't",
author = "Elke Neumann-Haefelin and Albrecht Kramer-Zucker and Krasimir Slanchev and Bj{\"o}rn Hartleben and Foteini Noutsou and Katrin Martin and Nicola Wanner and Alexander Ritter and Markus G{\"o}del and Philip Pagel and Xiao Fu and Alexandra M{\"u}ller and Ralf Baumeister and Gerd Walz and Huber, {Tobias B}",
year = "2010",
month = jun,
day = "15",
doi = "10.1093/hmg/ddq108",
language = "English",
volume = "19",
pages = "2347--59",
journal = "HUM MOL GENET",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "12",

}

RIS

TY - JOUR

T1 - A model organism approach

T2 - defining the role of Neph proteins as regulators of neuron and kidney morphogenesis

AU - Neumann-Haefelin, Elke

AU - Kramer-Zucker, Albrecht

AU - Slanchev, Krasimir

AU - Hartleben, Björn

AU - Noutsou, Foteini

AU - Martin, Katrin

AU - Wanner, Nicola

AU - Ritter, Alexander

AU - Gödel, Markus

AU - Pagel, Philip

AU - Fu, Xiao

AU - Müller, Alexandra

AU - Baumeister, Ralf

AU - Walz, Gerd

AU - Huber, Tobias B

PY - 2010/6/15

Y1 - 2010/6/15

N2 - Mutations of the immunoglobulin superfamily proteins nephrin and Neph1 lead to congenital nephrotic syndrome in humans or mice. Neph proteins are three closely related molecules that are evolutionarily conserved and mediate cell recognition. Their importance for morphogenetic processes including the formation of the kidney filtration barrier in vertebrates and synaptogenesis in Caenorhabditis elegans has recently been uncovered. However, the individual morphogenetic function of mammalian Neph1-3 isoforms remained elusive. We demonstrate now that the Neph/nephrin family proteins can form cell-cell adhesion modules across species. Expression of all three mammalian Neph isoforms partially rescued mutant C. elegans lacking their Neph homolog syg-1 and restored synapse formation, suggesting a functional redundancy between the three isoforms. Strikingly, the rescue of defective synaptic connectivity was prevented by deletion of the highly conserved cytoplasmic PSD95/Dlg/ZO-1-binding motif of SYG-1/Neph proteins, indicating the critical role of this intracellular signaling motif for SYG-1/Neph-dependent morphogenetic events. To determine the significance of Neph isoform redundancy for vertebrate kidney development, we analyzed the expression pattern and the functional role of Neph proteins in zebrafish. In situ hybridizations identified zNeph1 and zNeph2 as glomerular proteins. Morpholino knockdown of either zNeph1 or zNeph2 resulted in loss of slit diaphragms and leakiness of the glomerular filtration barrier. This is the first report utilizing C. elegans to study mammalian Neph/nephrin protein function and to demonstrate a functional overlap of Neph1-3 proteins. Furthermore, we identify Neph2 as a novel critical regulator of glomerular function, indicating that both Neph1 and Neph2 are required for glomerular maintenance and development.

AB - Mutations of the immunoglobulin superfamily proteins nephrin and Neph1 lead to congenital nephrotic syndrome in humans or mice. Neph proteins are three closely related molecules that are evolutionarily conserved and mediate cell recognition. Their importance for morphogenetic processes including the formation of the kidney filtration barrier in vertebrates and synaptogenesis in Caenorhabditis elegans has recently been uncovered. However, the individual morphogenetic function of mammalian Neph1-3 isoforms remained elusive. We demonstrate now that the Neph/nephrin family proteins can form cell-cell adhesion modules across species. Expression of all three mammalian Neph isoforms partially rescued mutant C. elegans lacking their Neph homolog syg-1 and restored synapse formation, suggesting a functional redundancy between the three isoforms. Strikingly, the rescue of defective synaptic connectivity was prevented by deletion of the highly conserved cytoplasmic PSD95/Dlg/ZO-1-binding motif of SYG-1/Neph proteins, indicating the critical role of this intracellular signaling motif for SYG-1/Neph-dependent morphogenetic events. To determine the significance of Neph isoform redundancy for vertebrate kidney development, we analyzed the expression pattern and the functional role of Neph proteins in zebrafish. In situ hybridizations identified zNeph1 and zNeph2 as glomerular proteins. Morpholino knockdown of either zNeph1 or zNeph2 resulted in loss of slit diaphragms and leakiness of the glomerular filtration barrier. This is the first report utilizing C. elegans to study mammalian Neph/nephrin protein function and to demonstrate a functional overlap of Neph1-3 proteins. Furthermore, we identify Neph2 as a novel critical regulator of glomerular function, indicating that both Neph1 and Neph2 are required for glomerular maintenance and development.

KW - Amino Acid Sequence

KW - Animals

KW - Caenorhabditis elegans

KW - Caenorhabditis elegans Proteins

KW - Cell Adhesion

KW - HeLa Cells

KW - Humans

KW - Immunoglobulins

KW - Kidney

KW - Membrane Proteins

KW - Mice

KW - Models, Animal

KW - Morphogenesis

KW - Neurons

KW - PDZ Domains

KW - Phylogeny

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/hmg/ddq108

DO - 10.1093/hmg/ddq108

M3 - SCORING: Journal article

C2 - 20233749

VL - 19

SP - 2347

EP - 2359

JO - HUM MOL GENET

JF - HUM MOL GENET

SN - 0964-6906

IS - 12

ER -