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PMID:19458237

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Citation

Lieberoth, A, Splittstoesser, F, Katagihallimath, N, Jakovcevski, I, Loers, G, Ranscht, B, Karagogeos, D, Schachner, M and Kleene, R (2009) Lewis(x) and alpha2,3-sialyl glycans and their receptors TAG-1, Contactin, and L1 mediate CD24-dependent neurite outgrowth. J. Neurosci. 29:6677-90

Abstract

Although carbohydrates have been implicated in cell interactions in the nervous system, the molecular bases of their functions have remained largely obscure. Here, we show that promotion or inhibition of neurite outgrowth of cerebellar or dorsal root ganglion neurons, respectively, induced by the mucin-type adhesion molecule CD24 depends on alpha2,3-linked sialic acid and Lewis(x) present on glia-specific CD24 glycoforms. Alpha2,3-sialyl residues of CD24 bind to a structural motif in the first fibronectin type III domain of the adhesion molecule L1. Following the observation that the adhesion molecules TAG-1 and Contactin show sequence homologies with fucose-specific lectins, we obtained evidence that TAG-1 and Contactin mediate Lewis(x)-dependent CD24-induced effects on neurite outgrowth. Thus, L1, TAG-1, and Contactin function as lectin-like neuronal receptors. Their cis interactions with neighboring adhesion molecules, e.g., Caspr1 and Caspr2, and with their triggered signal transduction pathways elicit cell type-specific promotion or inhibition of neurite outgrowth induced by glial CD24 in a glycan-dependent trans interaction.

Links

PubMed Online version:10.1523/JNEUROSCI.4361-08.2009

Keywords

Animals; Animals, Newborn; Antigens, CD15/pharmacology; Antigens, CD24/genetics; Antigens, CD24/metabolism; Binding Sites/drug effects; Cell Adhesion Molecules, Neuronal/deficiency; Cell Adhesion Molecules, Neuronal/physiology; Cells, Cultured; Cerebellum/cytology; Contactin 2; Contactins; Cricetinae; Cricetulus; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay/methods; Ganglia, Spinal/cytology; Glycosylation/drug effects; Immunoprecipitation/methods; Leukocyte L1 Antigen Complex/metabolism; Locomotion/genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurites/drug effects; Neurites/physiology; Neurons/classification; Neurons/cytology; Neurons/drug effects; Neurons/physiology; Peptides/pharmacology; Protein Binding/drug effects; Recovery of Function/genetics; Sialic Acids/pharmacology; Spinal Cord Injuries/genetics; Spinal Cord Injuries/pathology; Spinal Cord Injuries/physiopathology; Transfection/methods

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CNTP1

acts_upstream_of_or_within

GO:0031175: neuron projection development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:105980

P

  • occurs_in:(EMAPA:17787)
  • occurs_in:(CL:0000540)|occurs_in:(EMAPA:16668)
  • occurs_in:(CL:0000540)

Seeded From UniProt

complete

MOUSE:L1CAM

enables

GO:0033691: sialic acid binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:CNTN1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P24807

F

Seeded From UniProt

complete

MOUSE:CNTN1

acts_upstream_of_or_within

GO:0031175: neuron projection development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:104518
MGI:MGI:1858201
MGI:MGI:88323

P

  • occurs_in:(EMAPA:17787)
  • occurs_in:(CL:0000540)|occurs_in:(EMAPA:16668)
  • occurs_in:(CL:0000540)

Seeded From UniProt

complete

MOUSE:CNTN1

enables

GO:0030246: carbohydrate binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:CD24

acts_upstream_of_or_within

GO:0010976: positive regulation of neuron projection development

ECO:0000314: direct assay evidence used in manual assertion

P

  • regulates_o_occurs_in:(EMAPA:32845)
  • regulates_o_occurs_in:(CL:0000117)

Seeded From UniProt

complete

MOUSE:CD24

acts_upstream_of_or_within

GO:0010976: positive regulation of neuron projection development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:104518
MGI:MGI:105980

P

  • regulates_o_occurs_in:(EMAPA:32845)
  • regulates_o_occurs_in:(CL:0000540)|regulates_o_occurs_in:(EMAPA:16668)
  • regulates_o_occurs_in:(CL:0000540)

Seeded From UniProt

complete

MOUSE:CNTN2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P24807

F

Seeded From UniProt

complete

MOUSE:CNTP2

acts_upstream_of_or_within

GO:0031175: neuron projection development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:104518

P

  • occurs_in:(EMAPA:17787)
  • occurs_in:(CL:0000540)|occurs_in:(EMAPA:16668)
  • occurs_in:(CL:0000540)

Seeded From UniProt

complete

MOUSE:CNTN2

enables

GO:0030246: carbohydrate binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:CNTN2

acts_upstream_of_or_within

GO:0031175: neuron projection development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:105980
MGI:MGI:1914047
MGI:MGI:88323

P

  • occurs_in:(EMAPA:17787)
  • occurs_in:(CL:0000540)|occurs_in:(EMAPA:16668)
  • occurs_in:(CL:0000540)

Seeded From UniProt

complete


See also

References

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