Structure-function analysis of protein complexes involved in the molecular architecture of juxtaparanodal regions of myelinated fibers.
Demyelinating disorders, including multiple sclerosis (MS), are common causes of neurological disability. One critical step towards the management and therapy of demyelinating diseases is to understand the basic functions of myelinating glia and their relationship with axons. Axons and myelinating glia, oligodendrocytes in the central (CNS) and Schwann cells in the peripheral (PNS) nervous systems, reciprocally influence each other's development and trophism. These interactions are critical for the formation of distinct axonal domains in myelinated fibers that ensure the rapid propagation of action potentials. Macromolecular complexes mediating axo-glial interactions in these domains have been identified, consisting of members of the immunoglobulin superfamily (IgSF) of adhesion molecules and the neurexin/NCP superfamily as well as other proteins. We have investigated the molecular details of axo-glial interactions in the juxtaparanodal region of myelinated fibers by utilizing domain-specific GFP constructs and immunoprecipitation assays on transfected cells. We have shown that the immunoglobulin domains of the IgSF member TAG-1/Cnt-2 are necessary and sufficient for the direct, cis interaction of this protein with Caspr2 and potassium channels.
Tzimourakas
Alexandros
A
Department of Basic Science, Neuroscience Graduate Program, University of Crete Medical School, Heraklion, Crete, Greece.
Giasemi
Sevasti
S
Mouratidou
Maria
M
Karagogeos
Domna
D
D000818:Animals; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002460:Cell Line; D058969:Contactin 2; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000648:ultrastructure; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000648:ultrastructure*; D012584:Sciatic Nerve / Q000378:metabolism* / Q000648:ultrastructure*; D013329:Structure-Activity Relationship
C548674:CNTN2 protein, human; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; C548675:Cntn2 protein, mouse; D058969:Contactin 2; D006023:Glycoproteins; C482101:IGSF11 protein, human; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; C065171:cif nucleoside transporter