L1CAM interactions (Homo sapiens)
From WikiPathways
Description
The L1 family of cell adhesion molecules (L1CAMs) are a subfamily of the immunoglobulin superfamily of transmembrane receptors, comprised of four structurally related proteins: L1, Close Homolog of L1 (CHL1), NrCAM, and Neurofascin. These CAMs contain six Ig like domains, five or six fibronectin like repeats, a transmembrane region and a cytoplasmic domain. The L1CAM family has been implicated in processes integral to nervous system development, including neurite outgrowth, neurite fasciculation and inter neuronal adhesion.
L1CAM members are predominately expressed by neuronal, as well as some nonneuronal cells, during development. Except CHL1 all the other members of L1 family contain an alternatively spliced 12-nclueotide exon, encoding the amino acid residues RSLE in the neuronal splice forms but missing in the non-neuronal cells. The extracellular regions of L1CAM members are divergent and differ in their abilities to interact with extracellular, heterophilic ligands. The L1 ligands include other Ig-domain CAMs (such as NCAM, TAG-1/axonin and F11), proteoglycans type molecules (neurocan), beta1 integrins, and extra cellular matrix protein laminin, Neuropilin-1, FGF and EGF receptors. Some of these L1-interacting proteins also bind to other L1CAM members. For example TAG-1/axonin interact with L1 and NrCAM; L1, neurofascin and CHL1 binds to contactin family members. The cytoplasmic domains of L1CAM members are most highly conserved. Nevertheless, they have different cytoplasmic binding partners, and even those with similar binding partners may be involved in different signaling complexes and mechanisms. The most conserved feature of L1CAMs is their ability to interact with the actin cytoskeletal adapter protein ankyrin. The cytoplasmic ankyrin-binding domain, exhibits the highest degree of amino acid conservation throughout the L1 family.
L1CAM members are predominately expressed by neuronal, as well as some nonneuronal cells, during development. Except CHL1 all the other members of L1 family contain an alternatively spliced 12-nclueotide exon, encoding the amino acid residues RSLE in the neuronal splice forms but missing in the non-neuronal cells. The extracellular regions of L1CAM members are divergent and differ in their abilities to interact with extracellular, heterophilic ligands. The L1 ligands include other Ig-domain CAMs (such as NCAM, TAG-1/axonin and F11), proteoglycans type molecules (neurocan), beta1 integrins, and extra cellular matrix protein laminin, Neuropilin-1, FGF and EGF receptors. Some of these L1-interacting proteins also bind to other L1CAM members. For example TAG-1/axonin interact with L1 and NrCAM; L1, neurofascin and CHL1 binds to contactin family members. The cytoplasmic domains of L1CAM members are most highly conserved. Nevertheless, they have different cytoplasmic binding partners, and even those with similar binding partners may be involved in different signaling complexes and mechanisms. The most conserved feature of L1CAMs is their ability to interact with the actin cytoskeletal adapter protein ankyrin. The cytoplasmic ankyrin-binding domain, exhibits the highest degree of amino acid conservation throughout the L1 family.
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- He Y, Jensen GJ, Bjorkman PJ.; ''Cryo-electron tomography of homophilic adhesion mediated by the neural cell adhesion molecule L1.''; PubMed Europe PMC Scholia
- Maness PF, Schachner M.; ''Neural recognition molecules of the immunoglobulin superfamily: signaling transducers of axon guidance and neuronal migration.''; PubMed Europe PMC Scholia
- Tuvia S, Garver TD, Bennett V.; ''The phosphorylation state of the FIGQY tyrosine of neurofascin determines ankyrin-binding activity and patterns of cell segregation.''; PubMed Europe PMC Scholia
- Jacob J, Haspel J, Kane-Goldsmith N, Grumet M.; ''L1 mediated homophilic binding and neurite outgrowth are modulated by alternative splicing of exon 2.''; PubMed Europe PMC Scholia
- Kulahin N, Li S, Hinsby A, Kiselyov V, Berezin V, Bock E.; ''Fibronectin type III (FN3) modules of the neuronal cell adhesion molecule L1 interact directly with the fibroblast growth factor (FGF) receptor.''; PubMed Europe PMC Scholia
- Schmid RS, Midkiff BR, Kedar VP, Maness PF.; ''Adhesion molecule L1 stimulates neuronal migration through Vav2-Pak1 signaling.''; PubMed Europe PMC Scholia
- Nagaraj K, Hortsch M.; ''Phosphorylation of L1-type cell-adhesion molecules--ankyrins away!''; PubMed Europe PMC Scholia
- Zhao X, Yip PM, Siu CH.; ''Identification of a homophilic binding site in immunoglobulin-like domain 2 of the cell adhesion molecule L1.''; PubMed Europe PMC Scholia
- Arthur JS, Ley SC.; ''Mitogen-activated protein kinases in innate immunity.''; PubMed Europe PMC Scholia
- Herron LR, Hill M, Davey F, Gunn-Moore FJ.; ''The intracellular interactions of the L1 family of cell adhesion molecules.''; PubMed Europe PMC Scholia
- Schmid RS, Maness PF.; ''L1 and NCAM adhesion molecules as signaling coreceptors in neuronal migration and process outgrowth.''; PubMed Europe PMC Scholia
- Nishimura T, Fukata Y, Kato K, Yamaguchi T, Matsuura Y, Kamiguchi H, Kaibuchi K.; ''CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth.''; PubMed Europe PMC Scholia
- Koroll M, Rathjen FG, Volkmer H.; ''The neural cell recognition molecule neurofascin interacts with syntenin-1 but not with syntenin-2, both of which reveal self-associating activity.''; PubMed Europe PMC Scholia
- Schaefer AW, Kamiguchi H, Wong EV, Beach CM, Landreth G, Lemmon V.; ''Activation of the MAPK signal cascade by the neural cell adhesion molecule L1 requires L1 internalization.''; PubMed Europe PMC Scholia
- Wong EV, Schaefer AW, Landreth G, Lemmon V.; ''Casein kinase II phosphorylates the neural cell adhesion molecule L1.''; PubMed Europe PMC Scholia
- Kamiguchi H, Lemmon V.; ''Recycling of the cell adhesion molecule L1 in axonal growth cones.''; PubMed Europe PMC Scholia
- Whittard JD, Sakurai T, Cassella MR, Gazdoiu M, Felsenfeld DP.; ''MAP kinase pathway-dependent phosphorylation of the L1-CAM ankyrin binding site regulates neuronal growth.''; PubMed Europe PMC Scholia
- Zhang X, Davis JQ, Carpenter S, Bennett V.; ''Structural requirements for association of neurofascin with ankyrin.''; PubMed Europe PMC Scholia
- Schmid RS, Pruitt WM, Maness PF.; ''A MAP kinase-signaling pathway mediates neurite outgrowth on L1 and requires Src-dependent endocytosis.''; PubMed Europe PMC Scholia
- Peretti D, Peris L, Rosso S, Quiroga S, Cáceres A.; ''Evidence for the involvement of KIF4 in the anterograde transport of L1-containing vesicles.''; PubMed Europe PMC Scholia
- Islam R, Kristiansen LV, Romani S, Garcia-Alonso L, Hortsch M.; ''Activation of EGF receptor kinase by L1-mediated homophilic cell interactions.''; PubMed Europe PMC Scholia
- Tomatis VM, Trenchi A, Gomez GA, Daniotti JL.; ''Acyl-protein thioesterase 2 catalyzes the deacylation of peripheral membrane-associated GAP-43.''; PubMed Europe PMC Scholia
- Zhao X, Siu CH.; ''Colocalization of the homophilic binding site and the neuritogenic activity of the cell adhesion molecule L1 to its second Ig-like domain.''; PubMed Europe PMC Scholia
- Felding-Habermann B, Silletti S, Mei F, Siu CH, Yip PM, Brooks PC, Cheresh DA, O'Toole TE, Ginsberg MH, Montgomery AM.; ''A single immunoglobulin-like domain of the human neural cell adhesion molecule L1 supports adhesion by multiple vascular and platelet integrins.''; PubMed Europe PMC Scholia
- Kadmon G, Kowitz A, Altevogt P, Schachner M.; ''The neural cell adhesion molecule N-CAM enhances L1-dependent cell-cell interactions.''; PubMed Europe PMC Scholia
- Cheng L, Lemmon S, Lemmon V.; ''RanBPM is an L1-interacting protein that regulates L1-mediated mitogen-activated protein kinase activation.''; PubMed Europe PMC Scholia
- Gast D, Riedle S, Kiefel H, Müerköster SS, Schäfer H, Schäfer MK, Altevogt P.; ''The RGD integrin binding site in human L1-CAM is important for nuclear signaling.''; PubMed Europe PMC Scholia
- Kamiguchi H.; ''The mechanism of axon growth: what we have learned from the cell adhesion molecule L1.''; PubMed Europe PMC Scholia
- Volkmer H, Leuschner R, Zacharias U, Rathjen FG.; ''Neurofascin induces neurites by heterophilic interactions with axonal NrCAM while NrCAM requires F11 on the axonal surface to extend neurites.''; PubMed Europe PMC Scholia
- Kamiguchi H, Lemmon V.; ''Neural cell adhesion molecule L1: signaling pathways and growth cone motility.''; PubMed Europe PMC Scholia
- Kristiansen LV, Marques FA, Soroka V, Ronn LC, Kiselyov V, Pedersen N, Berezin V, Bock E.; ''Homophilic NCAM interactions interfere with L1 stimulated neurite outgrowth.''; PubMed Europe PMC Scholia
- Zheng CF, Guan KL.; ''Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2.''; PubMed Europe PMC Scholia
- Castellani V, De Angelis E, Kenwrick S, Rougon G.; ''Cis and trans interactions of L1 with neuropilin-1 control axonal responses to semaphorin 3A.''; PubMed Europe PMC Scholia
- Roskoski R.; ''MEK1/2 dual-specificity protein kinases: structure and regulation.''; PubMed Europe PMC Scholia
- Gauthier-Campbell C, Bredt DS, Murphy TH, El-Husseini Ael-D.; ''Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs.''; PubMed Europe PMC Scholia
- Kamiguchi H, Long KE, Pendergast M, Schaefer AW, Rapoport I, Kirchhausen T, Lemmon V.; ''The neural cell adhesion molecule L1 interacts with the AP-2 adaptor and is endocytosed via the clathrin-mediated pathway.''; PubMed Europe PMC Scholia
- Panicker AK, Buhusi M, Erickson A, Maness PF.; ''Endocytosis of beta1 integrins is an early event in migration promoted by the cell adhesion molecule L1.''; PubMed Europe PMC Scholia
- Needham LK, Thelen K, Maness PF.; ''Cytoplasmic domain mutations of the L1 cell adhesion molecule reduce L1-ankyrin interactions.''; PubMed Europe PMC Scholia
- Nishimura K, Akiyama H, Komada M, Kamiguchi H.; ''betaIV-spectrin forms a diffusion barrier against L1CAM at the axon initial segment.''; PubMed Europe PMC Scholia
- Sakurai T, Gil OD, Whittard JD, Gazdoiu M, Joseph T, Wu J, Waksman A, Benson DL, Salton SR, Felsenfeld DP.; ''Interactions between the L1 cell adhesion molecule and ezrin support traction-force generation and can be regulated by tyrosine phosphorylation.''; PubMed Europe PMC Scholia
- Nakata A, Kamiguchi H.; ''Serine phosphorylation by casein kinase II controls endocytic L1 trafficking and axon growth.''; PubMed Europe PMC Scholia
- Schaefer AW, Kamei Y, Kamiguchi H, Wong EV, Rapoport I, Kirchhausen T, Beach CM, Landreth G, Lemmon SK, Lemmon V.; ''L1 endocytosis is controlled by a phosphorylation-dephosphorylation cycle stimulated by outside-in signaling by L1.''; PubMed Europe PMC Scholia
- Grumet M, Edelman GM.; ''Neuron-glia cell adhesion molecule interacts with neurons and astroglia via different binding mechanisms.''; PubMed Europe PMC Scholia
- Horstkorte R, Schachner M, Magyar JP, Vorherr T, Schmitz B.; ''The fourth immunoglobulin-like domain of NCAM contains a carbohydrate recognition domain for oligomannosidic glycans implicated in association with L1 and neurite outgrowth.''; PubMed Europe PMC Scholia
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
ADP | Metabolite | 16761 (ChEBI) | |
ALCAM | Protein | Q13740 (UniProt) | |
AP2 clathrin:L1:KIF4:
microtubule | Complex | REACT_23331 (Reactome) | |
ATP | Metabolite | 15422 (ChEBI) | |
Activated ERK2 | Protein | P28482 (UniProt) | |
Ankyrin-G | Protein | P16157 (UniProt) | |
Ankyrins | Protein | REACT_22717 (Reactome) | |
Axonin-1 | Protein | Q02246 (UniProt) | |
CHL1 | Protein | O00533 (UniProt) | |
CHL1:
alpha1beta1/alpha2b eta1 integrins | Complex | REACT_22459 (Reactome) | |
CHL1:Ankyrin-G | Complex | REACT_23311 (Reactome) | |
CHL1:CNTN6 | Complex | REACT_23145 (Reactome) | |
CHL1:Hsc70 | Complex | REACT_22887 (Reactome) | |
CHL1:NP-1 | Complex | REACT_22777 (Reactome) | |
CNTN1 | Protein | Q12860 (UniProt) | |
CRMP-2:NUMB:alpha
adaptin | Complex | REACT_22454 (Reactome) | |
Casein kinase II | Complex | REACT_23098 (Reactome) | |
Clathrin-coated
vesicle | Complex | REACT_13103 (Reactome) | |
Contactin-6 | Protein | Q9UQ52 (UniProt) | |
Contactin1:CASPR
complex | Complex | REACT_23146 (Reactome) | |
Doublecortin | Protein | O43602 (UniProt) | |
Dynamin-1/2/3 | Protein | REACT_22651 (Reactome) | |
EGFR | Protein | P00533 (UniProt) | |
EPHB2 | Protein | P29323 (UniProt) | |
ERM:PIP2 | Complex | REACT_22835 (Reactome) | |
Endophilin | Protein | Q99962 (UniProt) | |
F-actin | Unknown | REACT_20433 (Reactome) | |
Fibroblast growth
factor receptor 1c | Protein | P11362-1 (UniProt) | |
GDP | Metabolite | 17552 (ChEBI) | |
GTP | Metabolite | 15996 (ChEBI) | |
Heat Stable Antigen
(HSA) | Protein | P25063 (UniProt) | |
Hsc70 | Protein | P31948 (UniProt) | |
Integrins | Complex | REACT_23070 (Reactome) | |
KIF4 dimer | Complex | REACT_23088 (Reactome) | |
L1 | Protein | P32004 (UniProt) | |
L1 dimer:Ankyrin:
Spectrin:F-actin | Complex | REACT_22451 (Reactome) | |
L1 homodimer | Complex | REACT_22876 (Reactome) | |
L1 trans-
homodimer:Ankyrin | Complex | REACT_22843 (Reactome) | |
L1 trans-homodimer | Complex | REACT_22570 (Reactome) | |
L1-EGFR trans-
heterodimer | Complex | REACT_22956 (Reactome) | |
L1:ALCAM | Complex | REACT_23036 (Reactome) | |
L1:AP-2 Clathrin
complex | Complex | REACT_22867 (Reactome) | |
L1:AP-2 Clathrin
complex | Complex | REACT_22916 (Reactome) | |
L1:Axonin-1 | Complex | REACT_23324 (Reactome) | |
L1:CNTN1 | Complex | REACT_23027 (Reactome) | |
L1:FGFR1 | Complex | REACT_22912 (Reactome) | |
L1:HNK-1 | Complex | REACT_23380 (Reactome) | |
L1:HSA | Complex | REACT_22674 (Reactome) | |
L1:Integrin complex | Complex | REACT_22722 (Reactome) | |
L1:Laminin | Complex | REACT_23226 (Reactome) | |
L1:NCAM1 complex | Complex | REACT_23047 (Reactome) | |
L1:NP-1 | Complex | REACT_23153 (Reactome) | |
L1:NUMB:CRMP-2:
alpha-adaptin | Complex | REACT_22785 (Reactome) | |
L1:Neurocan | Complex | REACT_23328 (Reactome) | |
L1:RanBPM | Complex | REACT_23100 (Reactome) | |
L1:clathrin-coated
vesicle | Complex | REACT_22698 (Reactome) | |
Laminin-1 (EHS
laminin) | Complex | REACT_14571 (Reactome) | |
MEK1:ERK-1 | Complex | REACT_5539 (Reactome) | |
MEK2:ERK-2 | Complex | REACT_5435 (Reactome) | |
NCAM1 | Protein | P13591 (UniProt) | |
NFASC:pNFASC | Complex | REACT_22522 (Reactome) | |
Na+/K+ channel
subunits | Complex | REACT_23061 (Reactome) | |
Neurocan | Protein | O14594 (UniProt) | |
Neurofascin | Protein | O94856 (UniProt) | |
Neurofascin:
Syntenin-1 complex | Complex | REACT_23202 (Reactome) | |
Neurofascin:Ankyrin-
G complex | Complex | REACT_22462 (Reactome) | |
Neurofascin:CNTN1:
CASPR complex | Complex | REACT_22948 (Reactome) | |
Neurofascin:NrCAM
complex | Complex | REACT_22606 (Reactome) | |
Neurofascin:NrCAM:
Ankyrin:spectrin based actin | Complex | REACT_23030 (Reactome) | |
Neurofascin:NrCAM:
Ankyrin:spectrin based actin:Na+/K+ channel | Complex | REACT_22749 (Reactome) | |
Neuropilin-1 | Protein | O14786-1 (UniProt) | |
Neuropilin-2 (NP2) | Protein | O60462 (UniProt) | |
NrCAM | Protein | Q92823 (UniProt) | |
NrCAM:Ankyrin-G | Complex | REACT_23219 (Reactome) | |
NrCAM:Axonin-1 | Complex | REACT_23383 (Reactome) | |
NrCAM:NP-2 | Complex | REACT_22473 (Reactome) | |
NrCAM:SAP
members | Complex | REACT_23321 (Reactome) | |
Orthophosphate | Metabolite | 18367 (ChEBI) | |
PAK1 | Protein | Q13153 (UniProt) | |
PAK1 dimer
(inactive/autoinhibited ) | Complex | REACT_23136 (Reactome) | |
RAC1-GDP | Complex | REACT_22018 (Reactome) | |
RAC1-GTP | Complex | REACT_21594 (Reactome) | |
RanBPM | Protein | Q96S59 (UniProt) | |
SRC | Protein | P12931-1 (UniProt) | |
Shootin-1 | Protein | A0MZ66 (UniProt) | |
Syntenin-1 | Protein | O00560 (UniProt) | |
Trans neurofascin
dimer:ankyrin-G | Complex | REACT_22613 (Reactome) | |
Tyr phos L1:EPHB2 | Complex | REACT_23011 (Reactome) | |
VAV2 | Protein | P52735 (UniProt) | |
alpha1beta1/alpha2b
eta1 | Complex | REACT_22630 (Reactome) | |
microtubule | Unknown | REACT_10446 (Reactome) | |
p-VAV2(Y172) | Protein | P52735 (UniProt) | |
p90rsk | Protein | REACT_23173 (Reactome) | |
pL1 (S1152):p90rsk:
clathrin-dynamin complex | Complex | REACT_23209 (Reactome) | |
pL1 (S1204, 1248):
ERK2:clathrin- dynamin complex | Complex | REACT_23286 (Reactome) | |
pL1 (Y1176) | Protein | P32004 (UniProt) | |
pL1 (Y1229):L1CAM | Complex | REACT_22871 (Reactome) | |
pL1:CK-II | Complex | REACT_22634 (Reactome) | |
pL1:ERM:F-actin | Complex | REACT_22519 (Reactome) | |
pL1:Ezrin | Complex | REACT_22884 (Reactome) | |
pL1:Shootin-1:F-
actin | Complex | REACT_22531 (Reactome) | |
pNFASC:Doublecortin | Complex | REACT_23013 (Reactome) | |
pPAK1:Rac1-GTP | Complex | REACT_23376 (Reactome) | |
phospho-ERK-1:
MEK1 | Complex | REACT_2796 (Reactome) | |
phospho-ERK-2:
MEK2 | Complex | REACT_3199 (Reactome) | |
spectrin based actin | Complex | REACT_22921 (Reactome) | |
synapse-associated
proteins (SAP) | Protein | REACT_23280 (Reactome) | |
unidentified protein
tyrosine kinase | Unknown | REACT_22532 (Reactome) | |
unknown protein | Unknown | REACT_22919 (Reactome) |
Annotated Interactions
No annotated interactions