Rapid Trimming of Cell Surface Polysialic Acid (PolySia) by Exovesicular Sialidase Triggers Release of Preexisting Surface Neurotrophin.
As acidic glycocalyx on primary mouse microglial cells and a mouse microglial cell line Ra2, expression of polysialic acid (polySia/PSA), a polymer of the sialic acid Neu5Ac (N-acetylneuraminic acid), was demonstrated. PolySia is known to modulate cell adhesion, migration, and localization of neurotrophins mainly on neural cells. PolySia on Ra2 cells disappeared very rapidly after an inflammatory stimulus. Results of knockdown and inhibitor studies indicated that rapid surface clearance of polySia was achieved by secretion of endogenous sialidase Neu1 as an exovesicular component. Neu1-mediated polySia turnover was accompanied by the release of brain-derived neurotrophic factor normally retained by polySia molecules. Introduction of a single oxygen atom change into polySia by exogenous feeding of the non-neural sialic acid Neu5Gc (N-glycolylneuraminic acid) caused resistance to Neu1-induced polySia turnover and also inhibited the associated release of brain-derived neurotrophic factor. These results indicate the importance of rapid turnover of the polySia glycocalyx by exovesicular sialidases in neurotrophin regulation.
From the Bioscience and Biotechnology Center and School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601, Japan.
Mizuki
M
Sumida
From the Bioscience and Biotechnology Center and School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601, Japan.
Masaya
M
Hane
From the Bioscience and Biotechnology Center and School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601, Japan.
Uichiro
U
Yabe
Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomiokamachi, Nagaoka 940-2188 Japan.
Yasushi
Y
Shimoda
Glycobiology Research and Training Center, Departments of Medicine and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0687.
Oliver M T
OM
Pearce
Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Makoto
M
Kiso
Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 981-8558, Sendai, Japan, and.
Taeko
T
Miyagi
Department of Brain Functions, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.
Makoto
M
Sawada
Glycobiology Research and Training Center, Departments of Medicine and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0687.
Ajit
A
Varki
From the Bioscience and Biotechnology Center and School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601, Japan, kitajima@agr.nagoya-u.ac.jp.
Ken
K
Kitajima
From the Bioscience and Biotechnology Center and School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601, Japan, chi@agr.nagoya-u.ac.jp.
Chihiro
C
Sato
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000201:enzymology*; D005455:Fluorescent Antibody Technique; D019276:Glycocalyx / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012794:Sialic Acids / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D012794:Sialic Acids; C021319:polysialic acid; D009439:Neuraminidase; D010100:Oxygen
Brain-derived Neurotrophic Factor (BDNF); Exosome; Microglia; N-Glycolyneuraminic Acid; Polysialic Acid; Polysialyltransferase; Sialic Acid; Sialidase