Disease relevance of L1cam

• L1 is involved in neuron-neuron adhesion, neurite fasciculation, outgrowth of neurites, cerebellar granule cell migration, neurite outgrowth on Schwann cells and interactions among epithelial cells of intestinal crypts [1].
• Mutations in the human L1 gene are associated with a variable phenotype, including mental retardation and anomalous development of the nervous system, referred to as 'CRASH' (corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraplegia, and hydrocephalus) [2].
• L1 is also expressed by many human carcinomas [3].
• In humans, mutations in the L1 gene are linked with a spectrum of brain disorders, including loss of the corticospinal tract, but the mechanistic basis for these disorders is unknown [4].
• The possible function of L1 in lymphoid cells was studied using subcloned ESb-MP lymphoma cells having high or low densities of L1 on the cell surface as well as activated splenic B lymphoblasts [5].

Psychiatry related information on L1cam

• In humans, mutations in the L1 cell adhesion molecule are associated with a neurological syndrome termed CRASH, which includes corpus callosum agenesis, mental retardation, adducted thumbs, spasticity, and hydrocephalus [6].

High impact information on L1cam

• The LINE-1 (L1) retrotransposon, the most important human mobile element, shapes the genome in many ways [7].
• In vitro, neurite outgrowth on an L1 substrate and fasciculation were impaired [2].
• L1 is involved in various recognition processes in the CNS and PNS, and binding to L1 can activate signal transduction pathways [2].
• NCAM, L1, and DCC--immunoglobulin cell adhesion molecules (Ig CAMs)--are widely expressed during development [8].
• Neural adhesion molecule L1 as a member of the immunoglobulin superfamily with binding domains similar to fibronectin [1].

Chemical compound and disease context of L1cam

• The results suggested that reactivity of MAb HPV-16.I23 to L1 protein is lost when leucine 152 of the HPV-16 L1 protein is replaced by phenylalanine [9].
• Increased antibody responses to human papillomavirus type 16 L1 protein expressed by recombinant vaccinia virus lacking serine protease inhibitor genes [10].
• In this work, we used a lactose-inducible system based on the Lactobacillus casei lactose operon promoter (plac) for expression of the HPV-16 L1 protein in L. casei [11].
• HPV antibody detection by ELISA with capsid protein L1 fused to glutathione S-transferase [12].
• The antibody also detects the HPV-16 L1 antigen in formalin fixed, paraffin wax embedded biopsy specimens and on routine cervical smears [13].

Biological context of L1cam

• Detailed physical mapping utilizing an available YAC contig encompassing the DXMit1 locus has localized the Mecp2 gene to a 40-kb region between the L1cam and the Rsvp loci, indicating the probable position of a homologue on the human X chromosome [14].
• YACs were isolated from four genomic libraries by PCR or hybridization screening for the loci Gabra3, DXHX1104, F8a, DXHX52, DXBay2, L1cam, and Rsvp [15].
• The cell adhesion molecule L1 mediates neurite outgrowth and fasciculation during embryogenesis and mutations in its gene have been linked to a number of human congenital syndromes [16].
• For optimal silencing of L1 gene expression by the NRSE-binding factor RE-1-silencing transcription factor (REST)/NRSF, both the NRSE and sequences in the first intron were required [16].
• Tissue-specific expression of the L1 cell adhesion molecule is modulated by the neural restrictive silencer element [16].

Anatomical context of L1cam

• A high density of signals for neuronal L1cam mRNA was found in the thalamus, mammillary body, and hippocampus [17].
• Surprisingly, many of the axon guidance defects present in the L1 knockout mice, such as abnormal corticospinal tract and corpus callosum, were not observed [18].
• We find that thalamocortical and corticothalamic axons in mice lacking L1 are hyperfasciculated, a subset of thalamocortical axons make pathfinding errors and thalamocortical axon growth cones are abnormally long in the subplate [19].
• Our main objective was to determine the role of L1 during the development of connections between thalamus and cortex [19].
• Regardless of their altered route, thalamic afferents in the reeler and L1 KO mice seem to be able to redistribute themselves on the cortical sheet and establish normal periphery-related representation in the somatosensory cortex [20].

Associations of L1cam with chemical compounds

• Some long projection neurons such as the pyramidal, mitral, principal neurons of several cranial nuclei, and presumably monoaminergic cells containing noradrenalin, dopamine, and serotonin, expressed high levels of L1cam [17].
• In vitro experiments showed that L1-L1 homophilic binding was lost, along with L1-alpha5beta1 integrin binding [18].
• Neurocan immunoreactivity was associated with the bromodeoxyuridine-positive cells in the superplate, as well as being present in oblique bands within the cortical plate, along which L1-bearing thalamic axons preferentially ran [21].
• L1-dependent neurite outgrowth of cerebellar neurons was inhibited by GM 6001, suggesting that proteolytic processing of L1 by a metalloprotease is involved in neurite outgrowth [22].
• L1 is a glycoprotein with an apparent molecular weight of 200 kDa in the developing fetus and adult central nervous system [23].

Physical interactions of L1cam

• These studies demonstrate that the L1/NP-1 complex is able to confer a biological response to Sema3A with L1 mediating receptor internalization following ligand activation [24].
• We demonstrate here that the paired domain and homeodomain containing Pax-6 protein binds to three different sites in the promoter region of the L1 gene [25].

Enzymatic interactions of L1cam

• This neuropsin-specific L1-cleaving system is involved in NMDA receptor-dependent synaptic plasticity, such as the Schaffer collateral long-term potentiation [26].

Co-localisations of L1cam

• 5. In contrast with its mRNA, the protein was intensely detected on the fasciculated axons in the floor plates, ventral root, and dorsal funiculus in the E10.5-11.5 spinal cord and colocalized with NCAM and L1 on the ventral root and dorsal funiculus and partly colocalized with TAG-1 on the commissural axons and dorsal funiculus [27].
• In the E18 cortex, L1 colocalized with microtubule-associated protein 2, a marker of dendrites and somata [6].

Regulatory relationships of L1cam

• The signal transduction pathways involved in adhesion molecule L1-triggered neuritogenesis and neuroprotection were investigated using the extracellular domain of mouse or human L1 in fusion with the Fc portion of human immunoglobulin G or L1 purified from mouse brain by affinity chromatography [28].
• We propose that ectodomain-released L1 promotes migration by autocrine/paracrine stimulation via alpha v beta 5 [3].
• All four mRNAs are expressed in NSC-34 cells, but only neurofascin and the insert-minus form of L1 are expressed in its neuroblastoma parent, N18TG2 [29].
• To dissociate the functional roles of L1 in the adult brain from developmental abnormalities, we have generated a mutant in which the L1 gene is inactivated by cre-recombinase under the control of the calcium/calmodulin-dependent kinase II promoter [30].
• The results demonstrate that NSSR1 promotes neuronal differentiation and the splicing of NCAML1 exon2 and TrkC-K1 [31].

Other interactions of L1cam

• These experiments show that the NRSE and REST/NRSF are important components in restricting L1 expression to the embryonic nervous system [16].
• In L1-minus mice at postnatal day 0, TH-positive cells were present abnormally in the dorsomedial mesencephalon, suggesting impaired migration [32].
• L1cam mRNA was distributed widely from the olfactory bulb to the upper cervical cord with an uneven localization pattern in adult brain [17].
• A binding site for homeodomain and Pax proteins is necessary for L1 cell adhesion molecule gene expression by Pax-6 and bone morphogenetic proteins [33].
• The proprotein convertase PC5A and a metalloprotease are involved in the proteolytic processing of the neural adhesion molecule L1 [22].

Analytical, diagnostic and therapeutic context of L1cam

• To explore the distribution of L1cam mRNA-containing cells, which are interpreted to be L1cam-producing cells, we performed in situ hybridization histochemistry with an antisense L1cam cRNA probe [17].
• Distribution of L1cam mRNA in the adult mouse brain: In situ hybridization and Northern blot analyses [17].
• These pathfinding defects were confirmed by immunohistochemistry for L1 and TAG1, markers of the early axonal connections [34].
• Using coculture assays, we report that Sema3A secreted from the ventral spinal cord repels cortical axons from wild-type but not from L1-deficient mice [35].
• Immunofluorescence analysis of the extracellular framework of the spleen, using an Ab to laminin, reveals that L1 knockout mice have an irregularly shaped, discontinuous white pulp margin [36].

References