IgLON cell adhesion molecules regulate synaptogenesis in hippocampal neurons

Hashimoto, Takashi; Maékawa, Shohei; Miyata, Seiji

doi:10.1002/cbf.1600

Cited by 91 publications

(82 citation statements)

References 15 publications

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“…Finally, Negr1 overexpression affects the number of synapses with different outcomes depending on the culture stage. If it occurs in early stages, the overexpression of Negr1 decreases the number of synapses, whereas at later stages it is positively associated with synapse number (37). The silencing approach described here sheds light on the physiological function of endogenous Negr1.…”

Section: Discussionmentioning

confidence: 90%

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A Cell Surface Biotinylation Assay to Reveal Membrane-associated Neuronal Cues: Negr1 Regulates Dendritic Arborization

Pischedda

Szczurkowska

Cirnaru

et al. 2014

Molecular & Cellular Proteomics

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A complex and still not comprehensively resolved panel of transmembrane proteins regulates the outgrowth and the subsequent morphological and functional development of neuronal processes. In order to gain a more detailed description of these events at the molecular level, we have developed a cell surface biotinylation assay to isolate, detect, and quantify neuronal membrane proteins. When we applied our assay to investigate neuron maturation in vitro, we identified 439 differentially expressed proteins, including 20 members of the immunoglobulin superfamily. Among these candidates, we focused on Negr1, a poorly described cell adhesion molecule. We demonstrated that Negr1 controls the development of neurite arborization in vitro and in vivo. Given the tight correlation existing among synaptic cell adhesion molecules, neuron maturation, and a number of neurological disorders, our assay results are a useful tool that can be used to support the understanding of the molecular bases of physiological and pathological brain function. Genetic analysis indicates that 20% to 30% of the total open reading frame encodes for integral membrane proteins (1). Although less abundant than cytosolic proteins, membrane-passing proteins contribute to the regulation of all major cell processes and signaling pathways. In particular, membrane proteins play an important role in the establishment of functional neuronal circuitries during development. This process initially entails the growth, guidance, and stabilization of neuronal processes (axons and dendrites) in a timely, ordered manner involving cell surface molecules that sense the extracellular surroundings and activate signaling cascades (2).Then, specialized cell-to-cell connections, the synapses, are formed. These connections allow information to flow from one neuron to another and relay the precise juxtaposition and interactions between the pre-and postsynaptic membrane proteins to support their final functional establishment. Several families of synaptic transmembrane or membrane proteins, such as semaphorin, neuroligin, neurexin, and the immunoglobulin superfamily (IgSF), 1 are implicated in neurite formation and synapse establishment (3). However, the picture of membrane proteins expressed in neurons is still far from being completely resolved, and it is expected that many other key molecules are awaiting identification (4). Thus, uncovering the nature of the dynamic multiprotein complexes expressed at the plasma membrane will possibly strongly support the understanding of the mechanism controlling structural and functional neuron development. Here, we describe a biochemical approach to isolate and quantify proteins exposed at the extracellular side of the plasma membrane. Our assay utilized affinity purification on streptavidin resin of biotinylated membrane proteins extracted from a crude synaptosomal preparation. We combined this cell surface biotinylation assay with MS/MS analysis and label-free quantification to investigate protein patterns characterizing immature and m...

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Section: Discussionmentioning

confidence: 90%

“…Negr1 belongs to a subgroup of the IgSF named IgLON. IgLON CAMs are implicated in synapse formation, functions, and plasticity (37). Given the expression profile we reported for in vitro culturing, we investigated the impact of Negr1 on neuronal morphological maturation.…”

Section: Fig 2 Cell Surface Biotinylation Assay Isolates Membrane Pmentioning

confidence: 99%

A Cell Surface Biotinylation Assay to Reveal Membrane-associated Neuronal Cues: Negr1 Regulates Dendritic Arborization

Pischedda

Szczurkowska

Cirnaru

et al. 2014

Molecular & Cellular Proteomics

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“…IgLON family members are also expressed at synaptic sites (22,40,43). Overexpression of individual IgLON family members differentially affects the number of dendritic synapses that form in cultured hippocampal neurons, whereas NEGR1 and OBCAM loss of function results in a reduction in synapse formation on dendrites (42,44,45). Proteolytic cleavage of IgLON family members could thus have critical roles in specific targeting and synaptogenesis of cortical neurons similar to roles of other synaptic cell adhesion molecules, including NCAM, L1-CAM, and N-cadherin (46 -48).…”

Section: Discussionmentioning

confidence: 99%

IgLON Cell Adhesion Molecules Are Shed from the Cell Surface of Cortical Neurons to Promote Neuronal Growth

Sanz

Ferraro

Fournier

2015

Journal of Biological Chemistry

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Background: Ectodomain shedding by the metalloproteinase family affects axon guidance and neurite outgrowth. Results: IgLON family members are metalloproteinase substrates that promote neurite outgrowth in a metalloproteinase-dependent manner. Conclusion: IgON family members are shed from the surface of cortical neurons to promote neurite extension. Significance: Proteolytic cleavage of IgLON family members could have critical roles in specific targeting and synaptogenesis in cortical neurons.

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“…The top two genes synergistically induced by TAZ/YAP⅐TEAD and TGF␤ identified in our analysis were NEGR1 and UCA1. NEGR1 encodes a cell adhesion molecule that plays a role in neuronal growth and development (53)(54)(55)(56)(57)(58)(59). UCA1 encodes a long noncoding RNA that is expressed in development, is turned off in homeostatic tissues, and has been found to be highly expressed in bladder carcinomas (60).…”

Section: Negr1 and Uca1 Are Direct Targets Of Teads And Are Necessarymentioning

confidence: 99%

The Transcriptional Regulators TAZ and YAP Direct Transforming Growth Factor β-induced Tumorigenic Phenotypes in Breast Cancer Cells

Hiemer

Szymaniak

Varelas

2014

Journal of Biological Chemistry

211

190

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Background:The TGF␤ and Hippo pathways are dysregulated in metastatic breast cancers. Results: TGF␤-induced cues and nuclear TAZ/YAP converge at the transcriptional level to control gene expression important for tumorigenesis. Conclusion: TAZ/YAP are required to promote TGF␤-induced tumorigenic phenotypes in breast cancer cells. Significance: Our study reveals novel cross-talk between the TGF␤ pathway and TAZ/YAP in late-stage breast cancers.

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IgLON cell adhesion molecules regulate synaptogenesis in hippocampal neurons

Cited by 91 publications

References 15 publications

A Cell Surface Biotinylation Assay to Reveal Membrane-associated Neuronal Cues: Negr1 Regulates Dendritic Arborization

A Cell Surface Biotinylation Assay to Reveal Membrane-associated Neuronal Cues: Negr1 Regulates Dendritic Arborization

IgLON Cell Adhesion Molecules Are Shed from the Cell Surface of Cortical Neurons to Promote Neuronal Growth

The Transcriptional Regulators TAZ and YAP Direct Transforming Growth Factor β-induced Tumorigenic Phenotypes in Breast Cancer Cells

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