A glycosynapse in myelin?
Myelin, the multilayered membrane which surrounds nerve axons, is the only example of a membranous structure where contact between extracellular surfaces of membrane from the same cell occurs. The two major glycosphingolipids (GSLs) of myelin, galactosylceramide (GalC) and its sulfated form, galactosylceramide I(3)-sulfate (SGC), can interact with each other by trans carbohydrate-carbohydrate interactions across apposed membranes. They occur in detergent-insoluble lipid rafts containing kinases and thus may be located in membrane signaling domains. These signaling domains may contact each other across apposed extracellular membranes, thus forming glycosynapses in myelin. Multivalent forms of these carbohydrates, GalC/SGC-containing liposomes, or galactose conjugated to albumin, have been added to cultured oligodendrocytes (OLs) to mimic interactions which might occur between these signaling domains when OL membranes or the extracellular surfaces of myelin come into contact. These interactions between multivalent carbohydrate and the OL membrane cause co-clustering or redistribution of myelin GSLs, GPI-linked proteins, several transmembrane proteins, and signaling proteins to the same membrane domains. They also cause depolymerization of the cytoskeleton, indicating that they cause transmission of a signal across the membrane. Their effects have similarities to those of anti-GSL antibodies on OLs, shown by others, suggesting that the multivalent carbohydrate interacts with GalC/SGC in the OL membrane. Communication between the myelin sheath and the axon regulates both axonal and myelin function and is necessary to prevent neurodegeneration. Participation of transient GalC and SGC interactions in glycosynapses between the apposed extracellular surfaces of mature compact internodal myelin might allow transmission of signals throughout the myelin sheath and thus facilitate myelin-axonal communication.
Division of Structural Biology and Biochemistry, Research Institute, Hospital for Sick Children, 555 University Ave., Toronto, ON, Canada M5G 1X8. jmboggs@sickkids.ca
Joan M
JM
Boggs
Huimin
H
Wang
Wen
W
Gao
Dina N
DN
Arvanitis
Yanping
Y
Gong
Weixian
W
Min
D000199:Actins / Q000378:metabolism; D000818:Animals; D002554:Cerebrosides / Q000737:chemistry / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005699:Galactosylceramides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D009186:Myelin Sheath / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D000199:Actins; D002554:Cerebrosides; D005699:Galactosylceramides; D008024:Ligands; C083015:cerebroside sulfate