Neurofascin regulates the formation of gephyrin clusters and their subsequent translocation to the axon hillock of hippocampal neurons

Burkarth, Nadine; Kriebel, Martin; Kranz, Eva Ursula; Volkmer, Hansjürgen

doi:10.1016/j.mcn.2007.06.001

Cited by 41 publications

(43 citation statements)

References 37 publications

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“…Although NF155 is found in glia, the neuronal NF186 isoform is tethered to the ankyrin-based cytoskeleton at AIS where it may serve as a organizer of the perineuronal net (14) and contributes to sodium channel clustering at the nodes of Ranvier (15,16). By contrast, NF166 is implicated in the induction of neurite outgrowth via FGFR1 signaling (17) and may be involved in the induction of gephyrin clusters in immature hippocampal neurons devoid of differentiated AIS (18). However, the role of neurofascin in the maintenance of inhibitory input in the adult brain is still unclear because of early mortality of neurofascin knock-out mice (16).…”

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confidence: 99%

The Cell Adhesion Molecule Neurofascin Stabilizes Axo-axonic GABAergic Terminals at the Axon Initial Segment

Kriebel

Metzger

Trinks

et al. 2011

Journal of Biological Chemistry

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Cell adhesion molecules regulate synapse formation and maintenance via transsynaptic contact stabilization involving both extracellular interactions and intracellular postsynaptic scaffold assembly. The cell adhesion molecule neurofascin is localized at the axon initial segment of granular cells in rat dentate gyrus, which is mainly targeted by chandelier cells. Lentiviral shRNA-mediated knockdown of neurofascin in adult rat brain indicates that neurofascin regulates the number and size of postsynaptic gephyrin scaffolds, the number of GABA A receptor clusters as well as presynaptic glutamate decarboxylase-positive terminals at the axon initial segment. By contrast, overexpression of neurofascin in hippocampal neurons increases gephyrin cluster size presumably via stimulation of fibroblast growth factor receptor 1 signaling pathways.

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confidence: 99%

The Cell Adhesion Molecule Neurofascin Stabilizes Axo-axonic GABAergic Terminals at the Axon Initial Segment

Kriebel

Metzger

Trinks

et al. 2011

Journal of Biological Chemistry

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“…4C). Proper expression of mutants was previously published (10). After transfection of wild type NF166 into PC12-E2 cells grown on a monolayer of neurofascin-expressing NIH/3T3 cells, the percentage of PC12-E2 cells elabo- rating neurites was increased to about 40%, whereas only 25% were achieved in the absence of neurofascin overexpression as a control (Fig.…”

Section: Fgfr1mentioning

confidence: 70%

“…Plasmids and Antibodies-cDNA expression vectors for chick neurofascin isoforms NF166 and NF186 as well as the NF166-CD and -ED mutants were described previously (7,10). NF166 point mutants and COOH-terminally truncated variants were constructed with the help of a QuikChange mutagenesis kit (Stratagene, Heidelberg, Germany).…”

Section: Methodsmentioning

confidence: 99%

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Analysis of Non-canonical Fibroblast Growth Factor Receptor 1 (FGFR1) Interaction Reveals Regulatory and Activating Domains of Neurofascin

Kirschbaum

Kriebel

Kranz

et al. 2009

Journal of Biological Chemistry

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Fibroblast growth factor receptors (FGFRs) are important for many different mechanisms, including cell migration, proliferation, differentiation, and survival. Here, we show a new link between FGFR1 and the cell adhesion molecule neurofascin, which is important for neurite outgrowth. After overexpression in HEK293 cells, embryonal neurofascin isoform NF166 was able to associate with FGFR1, whereas the adult isoform NF186, differing from NF166 in additional extracellular sequences, was deficient. Pharmacological inhibitors and overexpression of dominant negative components of the FGFR signaling pathway pointed to the activation of FGFR1 after association with neurofascin in neurite outgrowth assays in chick tectal neurons and rat PC12-E2 cells. Both extra-and intracellular domains of embryonal neurofascin isoform NF166 were able to form complexes with FGFR1 independently. However, the cytosolic domain was both necessary and sufficient for the activation of FGFR1. Cytosolic serine residues 56 and 100 were shown to be essential for the neurite outgrowth-promoting activity of neurofascin, whereas both amino acid residues were dispensable for FGFR1 association. In conclusion, the data suggest a neurofascin intracellular domain, which activates FGFR1 for neurite outgrowth, whereas the extracellular domain functions as an additional, regulatory FGFR1 interaction domain in the course of development.The four known fibroblast growth factor receptors (FGFRs), 2 which are targeted by a large family of 22 fibroblast growth factor ligands, represent a highly diverse signaling system important for migration, proliferation, differentiation, and survival of many different cell types (1, 2). fibroblast growth factor activation of FGFR leads to the activation of mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and phospholipase C␥ (PLC␥), depending on the cellular system under study. Non-canonical FGFR interactions with NCAM, cadherins, and syndecan via extracellular domains were also described (1). However, the contribution of intracellular interactions of FGFR1 with further membrane co-receptors is poorly understood. Only cytosolic interaction between FGFRs and EphA4 have been described that are involved in mutual transphosphorylation (3).The cell adhesion molecule neurofascin is important for cellcell communication in the nervous system (4, 5). Neurofascin regulates many different functions in the brain, suggesting that it functions as a key regulator for both developing and differentiated neural cells. Different alternatively spliced neurofascin isoforms are expressed in different cells and at different times of development (6). Embryonal neurofascin NF166 is important for neurite outgrowth and guidance (7,8). Recently, a role for neurofascin NF166 for early processes of inhibitory synaptogenesis at the axon hillock and for the positioning of inhibitory synapses at the axon initial segment has been proven (9, 10).In the more developed nervous system, NF166 is replaced by NF186, which is inhibitory...

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“…7) to the formation and maintenance of glycinergic synapse is sparse. Neurofascin, a member of the L1-family of adhesion proteins, was demonstrated to be essential for the generation of gephyrin clusters, as well as for the targeting of these clusters and of inhibitory synapse formation to the axon initial segment in Purkinje cells (Ango et al 2004;Burkarth et al 2007).…”

Section: Role Of Neuroligins In Gabaergic Synaptic Transmissionmentioning

confidence: 99%

Molecular architecture of glycinergic synapses

Dresbach

Nawrotzki

Kremer

et al. 2008

Histochem Cell Biol

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Synapses can be considered chemical machines, which are optimized for fast and repeated exocytosis of neurotransmitters from presynaptic nerve terminals and the reliable electrical or chemical transduction of neurotransmitter binding to the appropriate receptors in the postsynaptic membrane. Therefore, synapses share a common repertoire of proteins like, e.g., the release machinery and certain cell adhesion molecules. This basic repertoire must be extended in order to generate speciWcity of neurotransmission and allow plastic changes, which are considered the basis of developmental and/or learning processes. Here, we focus on these complementary molecules located in the presynaptic terminal and postsynaptic membrane specializations of glycinergic synapses. Moreover, as speciWcity of neurotransmission in this system is established by the speciWc binding of the neurotransmitter to its receptor, we review the molecular properties of glycine receptor subunits and their assembly into functional glycine receptors with diVerent functional characteristics. The past years have revealed that the molecular machinery underlying inhibitory and especially glycinergic postsynaptic membrane specializations is more complex and dynamic than previously anticipated from morphological studies. The emerging features include structural components as well as signaling modules, which could confer the plasticity required for the proper function of distinct motor and sensory functions.

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Neurofascin regulates the formation of gephyrin clusters and their subsequent translocation to the axon hillock of hippocampal neurons

Cited by 41 publications

References 37 publications

The Cell Adhesion Molecule Neurofascin Stabilizes Axo-axonic GABAergic Terminals at the Axon Initial Segment

The Cell Adhesion Molecule Neurofascin Stabilizes Axo-axonic GABAergic Terminals at the Axon Initial Segment

Analysis of Non-canonical Fibroblast Growth Factor Receptor 1 (FGFR1) Interaction Reveals Regulatory and Activating Domains of Neurofascin

Molecular architecture of glycinergic synapses

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