Protein 4.1B associates with both Caspr/paranodin and Caspr2 at paranodes and juxtaparanodes of myelinated fibres.
Caspr/paranodin, a neuronal transmembrane glycoprotein, is essential for the structure and function of septate-like paranodal axoglial junctions at nodes of Ranvier. A closely related protein, Caspr2, is concentrated in juxtaparanodal regions where it associates indirectly with the shaker-type potassium channels. Although ultrastructural studies indicate that paranodal complexes are linked to the cytoskeleton, the intracellular partners of Caspr/paranodin, as well as those of Caspr2, are poorly characterized. We show that the conserved intracellular juxtamembrane regions (GNP motif) of Caspr/paranodin and Caspr2 bind proteins 4.1R and 4.1B. 4.1B is known to be enriched in paranodal and juxtaparanodal regions. 4.1B immunoreactivity accumulates progressively at paranodes and juxtaparanodes during postnatal development, following the concentration of Caspr/paranodin and Caspr2, respectively, in central and peripheral myelinated axons. These two proteins coimmunoprecipitated with 4.1B in brain homogenates. Our results provide strong evidence for the association of 4.1B with Caspr/paranodin at paranodes and with Caspr2 at juxtaparanodes. We propose that 4.1B anchors these axonal proteins to the actin-based cytoskeleton in these two regions.
Denisenko-Nehrbass
Natalia
N
INSERM/UPMC U536, Institut du Fer à Moulin, 17, rue du Fer à Moulin, 75005 Paris, France.
Oguievetskaia
Ksénia
K
Goutebroze
Laurence
L
Galvez
Thierry
T
Yamakawa
Hisashi
H
Ohara
Osamu
O
Carnaud
Michèle
M
Girault
Jean-Antoine
JA
D000818:Animals; D001921:Brain / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D051663:Kv1.2 Potassium Channel; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009479:Neuropeptides; D015221:Potassium Channels / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism; D011901:Ranvier's Nodes / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*
C491323:CNTNAP1 protein, human; C403049:CNTNAP2 protein, human; D015816:Cell Adhesion Molecules, Neuronal; C105177:Cntnap1 protein, rat; D003598:Cytoskeletal Proteins; C496969:KCNA2 protein, human; C496972:Kcna2 protein, rat; D051663:Kv1.2 Potassium Channel; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins; D011956:Receptors, Cell Surface; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1