The cytoplasmic domain of the cell adhesion molecule L1 is not required for homophilic adhesion

Wong, Eric V.; Cheng, Guanghui; Payne, H. Ross; Lemmon, Vance

doi:10.1016/0304-3940(95)12100-i

Cited by 48 publications

(40 citation statements)

References 18 publications

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“…The wild-type (WT) human L1 (hL1) vector in pcDNA3 was described previously (Wong et al, 1995). The L1⌬RSLE, L1-1176, and L1-1180 were described previously .…”

Section: Methodsmentioning

confidence: 99%

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L1-Mediated Branching Is Regulated by Two Ezrin-Radixin-Moesin (ERM)-Binding Sites, the RSLE Region and a Novel Juxtamembrane ERM-Binding Region

2005

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We investigated how the neural cell adhesion molecule L1 mediates neurite outgrowth through L1-L1 homophilic interactions. Wild-type L1 and L1 with mutations in the cytoplasmic domain (CD) were introduced into L1 knock-out neurons, and transfected neurons were grown on an L1 substrate. Neurite length and branching were compared between wild-type L1 and L1CD mutations. Surprisingly, the L1CD is not required for L1-mediated neurite outgrowth but plays a critical role in neurite branching, through both the juxtamembrane region and the RSLE region. We demonstrate that both regions serve as ezrin-moesin-radixin-binding sites. A truncation mutant that deletes 110 of 114 amino acids of the L1CD still supports neurite outgrowth on an L1 substrate, suggesting that a coreceptor binds to L1 in cis and mediates neurite outgrowth and that L1-ankyrin interactions are not essential for neurite initiation or outgrowth. These data are consistent with a model in which L1 can influence L1-mediated neurite outgrowth and branching through both the L1CD and a coreceptor.

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“…The wild-type (WT) human L1 (hL1) vector in pcDNA3 was described previously (Wong et al, 1995). The L1⌬RSLE, L1-1176, and L1-1180 were described previously .…”

Section: Methodsmentioning

confidence: 99%

“…The L1⌬RSLE, L1-1176, and L1-1180 were described previously . The L1-1147 was described previously (Wong et al, 1995). The L1-4A and L1-1151YϾA constructs were generated by QuickChange XL-mutagenesis kit (Stratagene, La Jolla, CA) using the wild-type human L1 in pcDNA3 as the template.…”

Section: Methodsmentioning

confidence: 99%

L1-Mediated Branching Is Regulated by Two Ezrin-Radixin-Moesin (ERM)-Binding Sites, the RSLE Region and a Novel Juxtamembrane ERM-Binding Region

2005

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“…34. The rabbit anti-human L1 antibody has been described previously (35). The L1 cytoplasmic domain with a His 6 tag was expressed in Escherichia coli (28) and used to make a rabbit antibody.…”

Section: Methodsmentioning

confidence: 99%

Activation of the MAPK Signal Cascade by the Neural Cell Adhesion Molecule L1 Requires L1 Internalization

Schaefer¹,

Kamiguchi²,

Wong³

et al. 1999

Journal of Biological Chemistry

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168

171

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“…The RSLE-positive isoform is expressed predominantly in the CNS, and the RSLE domain may help sort Li to the axon growth cone . Homophilic binding of human Li is mediated by the second immunoglobulin domain of the extracellular portion of the molecule (Zhao and Siu, 1995); deletion of the cytoplasmic domain does not reduce adhesiveness (Hortsch et al, i995;Wong et al, 1995). Mutations in the gene for Li are associated with a spectrum of neurodevelopmental disorders characterized by mental retardation and combinations of aphasia, shuffling gait, adducted thumbs, spastic paraparesis, agenesis of the corpus callosum, hydrocephalus, pyramidal tract hypoplasia, and cerebellar dysplasia (Fransen et al, 1995).…”

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confidence: 99%

Characterization of Ethanol‐Sensitive and Insensitive Fibroblast Cell Lines Expressing Human L1

Wilkemeyer

Charness

1998

Journal of Neurochemistry

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Ethanol inhibits Li-mediated cell-cell adhesion in fibroblast cell lines stably transfected with human Li. Here we show that this action of ethanol is present in only a subset of transfected NIH/3T3 and L cell clonal cell lines. All Li-expressing cell lines had higher levels of cell adhesion than cell lines transfected with empty vector. In all ethanol-sensitive cell lines, Li -mediated adhesion was inhibited by ethanol (IC 50 5-iO mM), 2 mM butanol, but not 5 mM pentanol. In contrast, ethanolinsensitive cell lines were not inhibited by up to 200 mM ethanol, 2 mM butanol, or 5 mM pentanol. Ethanol sensitivity or insensitivity was a stable property of each cell line and was not associated with differences in electrophoretic mobility, abundance, or cell surface localization of Li. Fab fragments prepared from anti-Li polyclonal antisera inhibited cell adhesion only in the ethanol-sensitive cell lines. These data suggest that Li may exist in an alcohol-sensitive or an alcohol-insensitive state that may be governed by host cell factors. Key Words: Ethyl alcohol-Fetal alcohol syndrome-Cell adhesion molecule, Li -Cell transfection. J. Neurochem. 71, 2382Neurochem. 71, -239i (1998.The immunoglobulin neural cell adhesion molecule (N-CAM) Li plays a fundamental role in nervous system development (Hortsch, 1996). Li is expressed on axons and growth cones and binds to Li molecules on adjacent cells, components of the extracellular matrix, and cytoskeletal elements. Activation of Li initiates a signaling cascade involving the fibroblast growth factor receptor (Williams et al., i 994) and pp6O c-srr (1g nelzi et al., 1994), leading to changes in growth cone morphology and neurite outgrowth (Lemmon et al., 1989; Kamiguchi and Lemmon, i997). Two isoforms of Li are generated by alternate splicing of a 12-base pair segment in the cytoplasmic domain encoding the amino acids arginine, serine, leucine, and glutamic acid (RSLE) (Reid and Hemperly, i992). The RSLE-positive isoform is expressed predominantly in the CNS, and the RSLE domain may help sort Li to the axon growth cone . Homophilic binding of human Li is mediated by the second immunoglobulin domain of the extracellular portion of the molecule (Zhao and Siu, 1995); deletion of the cytoplasmic domain does not reduce adhesiveness (Hortsch et al., i995;Wong et al., 1995). Mutations in the gene for Li are associated with a spectrum of neurodevelopmental disorders characterized by mental retardation and combinations of aphasia, shuffling gait, adducted thumbs, spastic paraparesis, agenesis of the corpus callosum, hydrocephalus, pyramidal tract hypoplasia, and cerebellar dysplasia (Fransen et al., 1995).We noted previously a similarity in the neuropathology of Li mutations and fetal alcohol syndrome (FAS) (Ramanathan et al., 1996). Based on this observation, we studied the effects of ethanol on cell-cell interactions mediated by Li. Pharmacologically relevant concentrations of ethanol inhibited cell-cell adhesion in NG1O8-i5 cells treated with OP-l (an inducer of Li and...

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The cytoplasmic domain of the cell adhesion molecule L1 is not required for homophilic adhesion

Cited by 48 publications

References 18 publications

L1-Mediated Branching Is Regulated by Two Ezrin-Radixin-Moesin (ERM)-Binding Sites, the RSLE Region and a Novel Juxtamembrane ERM-Binding Region

L1-Mediated Branching Is Regulated by Two Ezrin-Radixin-Moesin (ERM)-Binding Sites, the RSLE Region and a Novel Juxtamembrane ERM-Binding Region

Activation of the MAPK Signal Cascade by the Neural Cell Adhesion Molecule L1 Requires L1 Internalization

Characterization of Ethanol‐Sensitive and Insensitive Fibroblast Cell Lines Expressing Human L1

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