Human netrin-G1 isoforms show evidence of differential expression

Meerabux, Joanne; Ohba, Hideki; Fukasawa, Masayuki; Suto, Yumiko; Aoki-Suzuki, Mika; Nishimura, Shigehiro; Itohara, Shigeyoshi; Yoshikawa, Takeo

doi:10.1016/j.ygeno.2005.04.004

Cited by 29 publications

(34 citation statements)

References 20 publications

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“…Netrins are extracellular, laminin-related proteins that provide guidance for migrating cells, and NTNG1 is a membrane-tethered glycophosphatidylinositol (GPI)-linked Netrin (Lai Wing Sun et al, 2011). Expression of NTNG1 has been reported in the adult human kidney by northern blot and semi-quantitative PCR (Meerabux et al, 2005) but its specific podocyte expression in the developing kidney has not been reported. The analysis also unveiled a novel list of PDZ domain proteins expressed in the mature podocytes, suggesting a role for these proteins in the establishment or maintenance of the slit diaphragm in mature human podocytes.…”

Section: Discussionmentioning

confidence: 99%

Single-cell analysis of progenitor cell dynamics and lineage specification in the human fetal kidney

et al. 2018

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The mammalian kidney develops through reciprocal interactions between the ureteric bud and the metanephric mesenchyme to give rise to the entire collecting system and the nephrons. Most of our knowledge of the developmental regulators driving this process arises from the study of gene expression and functional genetics in mice and other animal models. In order to shed light on human kidney development, we have used single-cell transcriptomics to characterize gene expression in different cell populations, and to study individual cell dynamics and lineage trajectories during development. Single-cell transcriptome analyses of 6414 cells from five individual specimens identified 11 initial clusters of specific renal cell types as defined by their gene expression profile. Further subclustering identifies progenitors, and mature and intermediate stages of differentiation for several renal lineages. Other lineages identified include mesangium, stroma, endothelial and immune cells. Novel markers for these cell types were revealed in the analysis, as were components of key signaling pathways driving renal development in animal models. Altogether, we provide a comprehensive and dynamic gene expression profile of the developing human kidney at the single-cell level.

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Section: Discussionmentioning

confidence: 99%

Single-cell analysis of progenitor cell dynamics and lineage specification in the human fetal kidney

et al. 2018

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“…Alternative splicing in netrin-G1 regulates NGL-1 and LAR binding Netrin-G1 displays extensive alternative splicing, mainly in the domain V region (Nakashiba et al, 2000;Nakashiba et al, 2002;Yin et al, 2002;Aoki-Suzuki et al, 2005;Meerabux et al, 2005;Eastwood and Harrison, 2008). In the fetal human brain, netrinG1c and netrin-G1d are most abundant (Fig.…”

Section: Domains Mediating the Cis Interaction Between Netrin-g1 And Larmentioning

confidence: 99%

Trans-induced cis interaction in the tripartite NGL-1, netrin-G1, and LAR adhesion complex promotes excitatory synaptic development

Song

Lee

Prosselkov

et al. 2013

Journal of Cell Science

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SummaryThe initial contact between axons and dendrites at early neuronal synapses is mediated by surface adhesion molecules and is thought to induce synaptic maturation through the recruitment of additional synaptic proteins. The initiation of synaptic maturation should be tightly regulated to ensure that synaptic maturation occurs selectively at subcellular sites of axo-dendritic adhesion. However, the underlying mechanism is poorly understood. Here, we report that the initial trans-synaptic adhesion mediated by presynaptic netrin-G1 and postsynaptic NGL-1 (netrin-G1 ligand-1) induces a cis interaction between netrin-G1 and the receptor protein tyrosine phosphatase LAR (leukocyte antigen-related), and that this promotes presynaptic differentiation. We propose that trans-synaptic adhesions at early neuronal synapses trigger recruitment of neighboring adhesion molecules in a cis manner in order to couple initial axo-dendritic adhesion with synaptic differentiation.

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“…Netrin Gs also differ from classical netrins in that they are found exclusively in vertebrates 1; 2; 6 , whereas classical netrins also have homologues in invertebrates and, additionally, netrin Gs fail to bind to the classical netrin receptors DCC and Unc5h 1; 2; 6 . Netrin G1 and netrin G2 each have multiple splice forms, 14 for netrin G1 (netrin G1a-o) and three for netrin G2 (netrin G2a-c), which differ by amino acid insertions of different lengths after domain LE1 or by deletion of different combinations of LE-domains 1; 6; 11 . For netrin G2, splice isoforms may contain an insertion of 59 (netrin G2b) or 34 amino acids (netrin G2c) between domains LE1 and LE2 (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…1) 1;6 . Expression of splice isoforms appears to be spatiotemporally regulated in the brain and, although very limited, expression outside the nervous system for some splice isoforms was found 11 .…”

Section: Introductionmentioning

confidence: 99%

Crystal Structure of the Ligand Binding Domain of Netrin G2

Brasch

Harrison

Ahlsén

et al. 2011

Journal of Molecular Biology

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Netrin G proteins represent a small family of synaptic cell adhesion molecules related to netrins and to the polymerization domains of laminins. Two netrin G proteins are encoded in vertebrate genomes, netrins G1and G2, which are known to bind the leucine-rich repeat proteins netrin G ligands (NGLs) 1 and 2, respectively. Netrin G proteins share a common multi-domain architecture comprising an laminin N-terminal (LN) domain followed by three Laminin-EGF (LE) domains and a C′ region containing a GPI anchor. Here we use deletion analysis to show that the LN domain region of netrin Gs contains the binding site for NGLs to which they bind with 1:1 stoichiometry and sub-micromolar affinity. Netrin Gs are alternatively spliced in their LE domain regions, but the binding region, the LN domain, is identical in all splice forms. We determined the crystal structure for a fragment comprising the LN domain and domain LE1 of Netrin G2 by Sulfur-SAD phasing and refined it to 1.8Å resolution. The structure reveals an overall architecture similar to laminin α chain LN domains, but includes significant differences including a Ca2+ binding site in the LN domain. These results reveal the minimal binding unit for interaction of netrin Gs with NGLs, define structural features specific to netrin Gs, and suggest that netrin G alternative splicing is not involved in NGL recognition.

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Human netrin-G1 isoforms show evidence of differential expression

Cited by 29 publications

References 20 publications

Single-cell analysis of progenitor cell dynamics and lineage specification in the human fetal kidney

Single-cell analysis of progenitor cell dynamics and lineage specification in the human fetal kidney

Trans-induced cis interaction in the tripartite NGL-1, netrin-G1, and LAR adhesion complex promotes excitatory synaptic development

Crystal Structure of the Ligand Binding Domain of Netrin G2

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