Association of Caspr/paranodin with tumour suppressor schwannomin/merlin and beta1 integrin in the central nervous system.
Caspr/paranodin is an essential neuronal component of paranodal axoglial junctions, associated with contactin/F3. Its short intracellular domain contains a conserved motif (GNP motif) capable of binding protein 4.1 domains [FERM domains (four point one, ezrin, radixin, moesin)]. Schwannomin/merlin is a tumour suppressor expressed in many cell types, including in neurons, the function and partners of which are still poorly characterized. We show that the FERM domain of schwannomin binds to the paranodin GNP motif in glutathione S-transferase (GST)-pull down assays and in transfected COS-7 cells. The two proteins co-immunoprecipitated in brain extracts. In addition, paranodin and schwannomin were associated with integrin beta1 in transfected cells and in brain homogenates. The presence of paranodin increased the association between integrin beta1 and schwannomin or its N-terminal domain, suggesting that the interactions between these proteins are interdependent. In jimpy mutant mice, which display a severe dysmyelination with deficient paranodal junctions, the interactions between paranodin, schwannomin and integrin beta1 were profoundly altered. Our results show that schwannomin and integrin beta1 can be associated with paranodin in the central nervous system. Since integrin beta1 and schwannomin do not appear to be enriched in paranodes they may be quantitatively minor partners of paranodin in these regions and/or be associated with paranodin at other locations.
Denisenko-Nehrbass
Natalia
N
INSERM/UPMC U536, Institut du Fer à Moulin, Paris, France.
Goutebroze
Laurence
L
Galvez
Thierry
T
Bonnon
Carine
C
Stankoff
Bruno
B
Ezan
Pascal
P
Giovannini
Marco
M
Faivre-Sarrailh
Catherine
C
Girault
Jean-Antoine
JA
D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D001059:Apoproteins / Q000235:genetics; D001923:Brain Chemistry; D019556:COS Cells; D015816:Cell Adhesion Molecules, Neuronal; D002490:Central Nervous System / Q000737:chemistry / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics; D019012:Integrin beta1 / Q000378:metabolism*; D046911:Macromolecular Substances; D051379:Mice; D008816:Mice, Jimpy; D008818:Mice, Neurologic Mutants; D018991:Myelin Proteolipid Protein / Q000235:genetics; D025581:Neurofibromin 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D011901:Ranvier's Nodes / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D001059:Apoproteins; D015816:Cell Adhesion Molecules, Neuronal; C491322:Cntnap1 protein, mouse; D019012:Integrin beta1; D046911:Macromolecular Substances; D018991:Myelin Proteolipid Protein; D025581:Neurofibromin 2; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase