Polysialic acid: versatile modification of NCAM, SynCAM 1 and neuropilin-2.
The glycan polysialic acid is well-known as a unique posttranslational modification of the neural cell adhesion molecule NCAM. Despite remarkable acceptor specificity, however, a few other proteins can be targets of polysialylation. Here, we recapitulate the biosynthesis of polysialic acid by the two polysialyltransferases ST8SIA2 and ST8SIA4 and highlight the increasing evidence that variation in the human ST8SIA2 gene is linked to schizophrenia and possibly other neuropsychiatric disorders. Moreover, we summarize the knowledge on the role of NCAM polysialylation in brain development gained by the analysis of NCAM- and polysialyltransferase-deficient mouse models. The last part of this review is focused on recent advances in identifying SynCAM 1 and neuropilin-2 as novel acceptors of polysialic acid in NG2 cells of the perinatal brain and in dendritic cells of the immune system, respectively.
Institute of Cellular Chemistry (4330), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Martina
M
Mühlenhoff
Manuela
M
Rollenhagen
Sebastian
S
Werneburg
Rita
R
Gerardy-Schahn
Herbert
H
Hildebrandt
D000818:Animals; D001921:Brain / Q000201:enzymology; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D002633:Chemotaxis / Q000502:physiology; D003713:Dendritic Cells / Q000502:physiology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D039943:Neuropilin-2 / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012794:Sialic Acids / Q000378:metabolism*; D012799:Sialyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D019006:Neural Cell Adhesion Molecules; D039943:Neuropilin-2; D012794:Sialic Acids; C021319:polysialic acid; C046778:CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase; C526452:ST8SiaII protein, mouse; D012799:Sialyltransferases; C525848:ST8SiaIV protein, mouse; C515117:ST8SIA4 protein, human