Promotion of neuronal cell adhesion by members of the IgLON family occurs in the absence of either support or modification of neurite outgrowth

McNamee, Christine J.; Reed, James E.; Howard, Mark; Lodge, Anthony P.; Moss, Darren M.

doi:10.1046/j.0022-3042.2002.00798.x

Cited by 33 publications

(24 citation statements)

References 29 publications

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“…In some cases, little or no response has been observed and, in others, moderate enhancement or inhibition has been seen (Gil et al, 1998;Hancox et al, 1997;Lodge et al, 2001;Mann et al, 1998;Marg et al, 1999;McNamee et al, 2002). Interestingly, the most striking results were obtained with GP55, a glycoprotein isolated from adult brain that contains a mixture of all members of the IgLON family (Clarke and Moss, 1994).…”

mentioning

confidence: 79%

Diglons are heterodimeric proteins composed of IgLON subunits, and Diglon-CO inhibits neurite outgrowth from cerebellar granule cells

Reed

McNamee

Rackstraw

et al. 2004

Journal of Cell Science

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IgLONs are a family of four cell adhesion molecules belonging to the Ig superfamily that are thought to play a role in cell-cell recognition and growth-cone migration. One member of the family, opioid-binding cell-adhesion molecule (OBCAM), might act as a tumour suppressor. Previous work has shown that limbic-system-associated protein (LAMP), CEPU-1/Neurotrimin and OBCAM interact homophilically and heterophilically within the family. Here, we show that, based on their relative affinities, CEPU-1 might be both a homo- and a heterophilic cell adhesion molecule, whereas LAMP and OBCAM act only as heterophilic cell adhesion molecules. A binding assay using recombinant IgLONs fused to human Fc showed that IgLONs are organized in the plane of the membrane as heterodimers, and we propose that IgLONs function predominantly as subunits of heterodimeric proteins (Diglons). Thus, the four IgLONs can form six Diglons. Furthermore, although singly transfected cell lines have little effect on neurite outgrowth, CHO cell lines expressing both CEPU-1 and OBCAM (Diglon-CO) inhibit neurite outgrowth from cerebellar granule cells.

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mentioning

confidence: 79%

Diglons are heterodimeric proteins composed of IgLON subunits, and Diglon-CO inhibits neurite outgrowth from cerebellar granule cells

Reed

McNamee

Rackstraw

et al. 2004

Journal of Cell Science

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“…Neurotrimin and LAMP are members of the IgLON family of immunoglobulin domain-containing glycosylphosphatidylinositolanchored cell adhesion molecules. These proteins are expressed in neurons and function in the development and stabilization of synapses (Gil et al, 1998(Gil et al, , 2002Hashimoto et al, 2009;McNamee et al, 2002;Sanz et al, 2015). Our results suggest that branched sialylated A2G´2F is expressed in synapses on carrier proteins, like calreticulin, neurotrimin and LAMP, and this N-glycan may contribute to synapse formation, maintenance and pruning.…”

Section: Discussionmentioning

confidence: 89%

“…However, there are few reports of the localization of calreticulin in the brain, where neurotrimin and LAMP are known to be synaptic proteins contributing to synapse formation (Gil et al, 1998(Gil et al, , 2002Hashimoto et al, 2009;McNamee et al, 2002;Sanz et al, 2015). To examine calreticulin localization in the brain, western blot analysis of subcellular fractionated samples of 12w mouse brain was performed.…”

Section: A2g´2f and Calreticulin Are Accumulated In Mouse Brain Synapmentioning

confidence: 99%

Branched Sialylated <i>N</i>-glycans Are Accumulated in Brain Synaptosomes and Interact with Siglec-H

Handa-Narumi

Yoshimura

Konishi

et al. 2018

Cell Struct. Funct.

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Proper N-glycosylation of proteins is important for normal brain development and nervous system function. Identification of the localization, carrier proteins and interacting partners of N-glycans is essential for understanding the roles of glycoproteins. The present study examined the N-glycan A2G´2F (Galβ1-3GlcNAcβ1-A2G´2F has a branched sialic acid structural feature, and branched sialylated A2G´2F is a major N-glycan in the mouse brain. Its expression in the mouse brain increases during development, suggesting that branched sialylated N-glycans play essential roles during brain development. However, the carrier proteins, interacting partners and localization of branched sialylated N-glycans remain unknown. We previously improved our method for analyzing N-glycans from trace samples, and here we succeeded in detecting A2G´2F in small fragments excised from the two-dimensional electrophoresis gels of subcellular fractionated mouse brain proteins. A2G´2F was accumulated in mouse brain synaptosomes. We identified calreticulin as one of the candidate A2G´2F carriers and found calreticulin expression in both the endoplasmic reticulum and synaptosomal fractions. Calreticulin was observed in dendritic spines of cultured cortical neurons. 6Synthesized branched sialylated glycan clusters interacted with sialic acid-binding immunoglobulin-like lectin H (Siglec-H), which is known to be a microglia-specific molecule. Taken together, these results suggest that branched sialylated A2G´2F in synaptosomes plays a role in the interaction of dendritic spines with microglia.

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“…Other significant nearby SNPs rs3101366, rs2568598 The function of Kilon/NEGR1 has been disputed since its initial description, with some suggesting it is primarily involved in cell-cell adhesion [71] , while others maintain a function in neurite outgrowth and synaptogenesis [75,109] . In situ hybridisation has been used to analyse the distribution of Kilon/NEGR1 in the developing and adult rat hippocampus, compared to the distribution of LAMP [11] .…”

Section: Snp Rs2815752mentioning

confidence: 99%

Functional Analysis of Seven Genes Linked to Body Mass Index and Adiposity by Genome-Wide Association Studies: A Review

Speakman

2013

Hum Hered

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Genome-wide association studies (GWAS) have identified a total of about 40 single nucleotide polymorphisms (SNPs) that show significant linkage to body mass index, a widely utilised surrogate measure of adiposity. However, only 8 of these associations have been confirmed by follow-up GWAS using more sophisticated measures of adiposity (computed tomography). Among these 8, there is a SNP close to the gene FTO which has been the subject of considerable work to diagnose its function. The remaining 7 SNPs are adjacent to, or within, the genes NEGR1, TMEM18, ETV5, FLJ35779, LINGO2, SH2B1 and GIPR, most of which are less well studied than FTO, particularly in the context of obesity. This article reviews the available data on the functions of these genes, including information gleaned from studies in humans and animal models. At present, we have virtually no information on the putative mechanism associating the genes FLJ35779 and LINGO2 to obesity. All of these genes are expressed in the brain, and for 2 of them (SH2B1 and GIPR), a direct link to the appetite regulation system is known. SH2B1 is an enhancer of intracellular signalling in the JAK-STAT pathway, and GIPR is the receptor for an appetite-linked hormone (GIP) produced by the alimentary tract. NEGR1, ETV5 and SH2B1 all have suggested roles in neurite outgrowth, and hence SNPs adjacent to these genes may affect development of the energy balance circuitry. Although the genes have central patterns of gene expression, implying a central neuronal connection to energy balance, for at least 4 of them (NEGR1, TMEM18, SH2B1 and GIPR), there are also significant peripheral functions related to adipose tissue biology. These functions may contribute to their effects on the obese phenotype.

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Promotion of neuronal cell adhesion by members of the IgLON family occurs in the absence of either support or modification of neurite outgrowth

Cited by 33 publications

References 29 publications

Diglons are heterodimeric proteins composed of IgLON subunits, and Diglon-CO inhibits neurite outgrowth from cerebellar granule cells

Diglons are heterodimeric proteins composed of IgLON subunits, and Diglon-CO inhibits neurite outgrowth from cerebellar granule cells

Branched Sialylated <i>N</i>-glycans Are Accumulated in Brain Synaptosomes and Interact with Siglec-H

Functional Analysis of Seven Genes Linked to Body Mass Index and Adiposity by Genome-Wide Association Studies: A Review

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