Retinal Proteoglycans Act as Cellular Receptors for Basement Membrane Assembly to Control Astrocyte Migration and Angiogenesis.
The basement membrane is crucial for cell polarity, adhesion, and motility, but how it is assembled on the cell surface remains unclear. Here, we find that ablation of glycosaminoglycan (GAG) side chains of proteoglycans in the neuroretina disrupts the retinal basement membrane, leading to arrested astrocyte migration and reduced angiogenesis. Using genetic deletion and time-lapse imaging, we show that retinal astrocytes require neuronal-derived PDGF as a chemoattractive cue and the retinal basement membrane as a migratory substrate. Genetic ablation of heparan sulfates does not produce the same defects as GAG null mutants. In contrast, enzymatic removal of heparan sulfates and chondroitin sulfates together inhibits de novo laminin network assembly. These results indicate that both heparan and chondroitin sulfate proteoglycans participate in retinal basement membrane assembly, thus promoting astrocyte migration and angiogenesis.
Departments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Chenqi
C
Tao
Departments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, NY 10032, USA. Electronic address: xz2369@columbia.edu.
Xin
X
Zhang
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism*; D001485:Basement Membrane / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D002809:Chondroitin Sulfates / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D018919:Neovascularization, Physiologic; D009474:Neurons / Q000378:metabolism; D009928:Organ Specificity; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D012162:Retinal Degeneration / Q000473:pathology; D015398:Signal Transduction; D014533:Uridine Diphosphate Glucose Dehydrogenase / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D002809:Chondroitin Sulfates; D006497:Heparan Sulfate; D010982:Platelet-Derived Growth Factor; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D014533:Uridine Diphosphate Glucose Dehydrogenase; D018631:ras Proteins
PDGF; angiogenesis; astrocyte; basement membrane; chondroitin sulfate; glycosaminoglycan; heparin sulfate; inner limiting membrane; proteoglycans; retina