RT Journal Article
SR Electronic
T1 The Expression of TAG-1 in Glial Cells Is Sufficient for the Formation of the Juxtaparanodal Complex and the Phenotypic Rescue of Tag-1 Homozygous Mutants in the CNS
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 13943
OP 13954
DO 10.1523/JNEUROSCI.2574-10.2010
VO 30
IS 42
A1 Maria Savvaki
A1 Kostas Theodorakis
A1 Lida Zoupi
A1 Antonis Stamatakis
A1 Simona Tivodar
A1 Kyriacos Kyriacou
A1 Fotini Stylianopoulou
A1 Domna Karagogeos
YR 2010
UL http://www.jneurosci.org/content/30/42/13943.abstract
AB Myelinated fibers are organized into specialized domains that ensure the rapid propagation of action potentials and are characterized by protein complexes underlying axoglial interactions. TAG-1 (Transient Axonal Glycoprotein-1), a cell adhesion molecule of the Ig superfamily, is expressed by neurons as well as by myelinating glia. It is essential for the molecular organization of myelinated fibers as it maintains the integrity of the juxtaparanodal region through its interactions with Caspr2 and the voltage-gated potassium channels (VGKCs) on the axolemma. Since TAG-1 is the only known component of the juxtaparanodal complex expressed by the glial cell, it is important to clarify its role in the molecular organization of juxtaparanodes. For this purpose, we generated transgenic mice that exclusively express TAG-1 in oligodendrocytes and lack endogenous gene expression (Tag-1−/−;plpTg(rTag-1)). Phenotypic analysis clearly demonstrates that glial TAG-1 is sufficient for the proper organization and maintenance of the juxtaparanodal domain in the CNS. Biochemical analysis shows that glial TAG-1 physically interacts with Caspr2 and VGKCs. Ultrastructural and behavioral analysis of Tag-1−/−;plpTg(rTag-1) mice shows that the expression of glial TAG-1 is sufficient to restore the axonal and myelin deficits as well as the behavioral defects observed in Tag-1−/− animals. Together, these data highlight the pivotal role of myelinating glia on axonal domain differentiation and organization.