The adhesion molecule Necl-3/SynCAM-2 localizes to myelinated axons, binds to oligodendrocytes and promotes cell adhesion.
BACKGROUND
Cell adhesion molecules are plasma membrane proteins specialized in cell-cell recognition and adhesion. Two related adhesion molecules, Necl-1 and Necl-2/SynCAM, were recently described and shown to fulfill important functions in the central nervous system. The purpose of the work was to investigate the distribution, and the properties of Necl-3/SynCAM-2, a previously uncharacterized member of the Necl family with which it shares a conserved modular organization and extensive sequence homology.


RESULTS
We show that Necl-3/SynCAM-2 is a plasma membrane protein that accumulates in several tissues, including those of the central and peripheral nervous system. There, Necl-3/SynCAM-2 is expressed in ependymal cells and in myelinated axons, and sits at the interface between the axon shaft and the myelin sheath. Several independent assays demonstrate that Necl-3/SynCAM-2 functionally and selectively interacts with oligodendrocytes. We finally prove that Necl-3/SynCAM-2 is a bona fide adhesion molecule that engages in homo- and heterophilic interactions with the other Necl family members, leading to cell aggregation.


CONCLUSIONS
Collectively, our manuscripts and the works on Necl-1 and SynCAM/Necl-2 reveal a complex set of interactions engaged in by the Necl proteins in the nervous system. Our work also support the notion that the family of Necl proteins fulfils key adhesion and recognition functions in the nervous system, in particular between different cell types.
Pellissier
François
F
Department of Biochemistry, University of Geneva, 30 Quai Ernest Ansermet, Sciences II, 1211 Geneva 4, Switzerland. francois.pellissier@biochem.unige.ch
Gerber
Alan
A
Bauer
Christoph
C
Ballivet
Marc
M
Ossipow
Vincent
V
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D004331:Drosophila melanogaster; D004805:Ependyma / Q000378:metabolism / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D007136:Immunoglobulins; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D009186:Myelin Sheath / Q000378:metabolism / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000378:metabolism* / Q000648:ultrastructure; D010525:Peripheral Nerves / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
C465040:Cadm1 protein, rat; C526756:Cadm2 protein, rat; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D007136:Immunoglobulins; D008565:Membrane Proteins; D020033:Protein Isoforms; D025521:Tumor Suppressor Proteins