Chondroitin sulfate proteoglycan phosphacan associates with parallel fibers and modulates axonal extension and fasciculation of cerebellar granule cells.
Phosphacan is a nervous system-specific chondroitin sulfate proteoglycan and one of the major components of extracellular matrix in the brain. In the present study, we examined its spatiotemporal expression, ultrastructural localization, binding manner, and in vitro analysis on cell adhesion, axonal extension, and fasciculation in rat cerebellum. The present light microscopic immunohistochemistry showed that phosphacan immunoreactivity was localized mainly at the molecular layer in the cerebellum, but not at the external granular layer. Further double labeling immunohistochemical and immunoelectron microscopic studies revealed that phosphacan was localized around parallel fibers, but not at synapses. The binding of phosphacan to membrane and/or extracellular matrix partly required Ca2+ and was mediated through its core glycoprotein. Phosphacan inhibited adhesion and axonal extension of cerebellar granule cells in dissociated culture, while it promoted axonal fasciculation of their aggregated culture. These results indicate that phosphacan around parallel fibers may be the repulsive substratum for adhesion and extension of granule cells and promote the fasciculation of parallel fibers.
Hayashi
Noriko
N
Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
Mizusaki
Maki J
MJ
Kamei
Kaeko
K
Harada
Shigeharu
S
Miyata
Seiji
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002525:Cerebellar Cortex / Q000254:growth & development* / Q000378:metabolism* / Q000648:ultrastructure; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D016253:Microscopy, Immunoelectron; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D013570:Synaptic Membranes / Q000378:metabolism / Q000648:ultrastructure
D011508:Chondroitin Sulfate Proteoglycans; D012333:RNA, Messenger; C516897:Ptprz1 protein, rat; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D002118:Calcium