Dataset Information

L1-mediated branching is regulated by two ezrin-radixin-moesin (ERM)-binding sites, the RSLE region and a novel juxtamembrane ERM-binding region.

ABSTRACT: 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.

SUBMITTER: Cheng L

PROVIDER: S-EPMC2860578 | biostudies-literature | 2005 Jan

REPOSITORIES: biostudies-literature

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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.

Cheng Ling L Itoh Kouichi K Lemmon Vance V

The Journal of neuroscience : the official journal of the Society for Neuroscience 20050101 2

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 ...[more]

PMID: 15647482

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Project description:BackgroundEndothelial junctions control functions such as permeability, angiogenesis and contact inhibition. VE-Cadherin (VECad) is essential for the maintenance of intercellular contacts. In confluent endothelial monolayers, N-Cadherin (NCad) is mostly expressed on the apical and basal membrane, but in the absence of VECad it localizes at junctions. Both cadherins are required for vascular development. The intercellular adhesion molecule (ICAM)-2, also localized at endothelial junctions, is involved in leukocyte recruitment and angiogenesis.ResultsIn human umbilical vein endothelial cells (HUVEC), both VECad and NCad were found at nascent cell contacts of sub-confluent monolayers, but only VECad localized at the mature junctions of confluent monolayers. Inhibition of ICAM-2 expression by siRNA caused the appearance of small gaps at the junctions and a decrease in NCad junctional staining in sub-confluent monolayers. Endothelioma lines derived from WT or ICAM-2-deficient mice (IC2neg) lacked VECad and failed to form junctions, with loss of contact inhibition. Re-expression of full-length ICAM-2 (IC2 FL) in IC2neg cells restored contact inhibition through recruitment of NCad at the junctions. Mutant ICAM-2 lacking the binding site for ERM proteins (IC2 ?ERM) or the cytoplasmic tail (IC2 ?TAIL) failed to restore junctions. ICAM-2-dependent Rac-1 activation was also decreased in these mutant cell lines. Barrier function, measured in vitro via transendothelial electrical resistance, was decreased in IC2neg cells, both in resting conditions and after thrombin stimulation. This was dependent on ICAM-2 signalling to the small GTPase Rac-1, since transendothelial electrical resistance of IC2neg cells was restored by constitutively active Rac-1. In vivo, thrombin-induced extravasation of FITC-labeled albumin measured by intravital fluorescence microscopy in the mouse cremaster muscle showed that permeability was increased in ICAM-2-deficient mice compared to controls.ConclusionsThese results indicate that ICAM-2 regulates endothelial barrier function and permeability through a pathway involving N-Cadherin, ERMs and Rac-1.

Dataset Information

L1-mediated branching is regulated by two ezrin-radixin-moesin (ERM)-binding sites, the RSLE region and a novel juxtamembrane ERM-binding region.

Publications

L1-mediated branching is regulated by two ezrin-radixin-moesin (ERM)-binding sites, the RSLE region and a novel juxtamembrane ERM-binding region.

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