NEUROCAN AND PHOSPHACAN - 2 MAJOR NERVOUS TISSUE-SPECIFIC CHONDROITINSULFATE PROTEOGLYCANS

Neurocan is a multidomain hyaluronan-binding chondroitin sulfate prote oglycan that is synthesized by neurons, whereas the astroglial proteog lycan phosphacan is an mRNA splice variant representing the entire ext racellular portion of a receptor-type protein tyrosine phosphatase. A glycoform of phosphacan (phosphacan-KS) that contains both chondroitin sulfate and keratan sulfate is present in the postnatal rat central n ervous system (CNS). The concentration of neurocan in brain increases during late embryonic development but then declines steeply during the early postnatal period together with hyaluronan, and neurocan also un dergoes extensive proteolytic processing during the course of brain de velopment. In contrast, the concentrations of both phosphacan and phos phacan-KS rise steadily after embryonic day 20 to reach a plateau at a bout 2 weeks postnatally. In the embryonic CNS the distribution of neu rocan mRNA is more widespread than that of phosphacan, which is primar ily present in regions of active cell proliferation. Neurocan mRNA is also present in areas where the proteoglycan is not expressed, and the re is evidence that the short open reading frame in its 5'-leader may function as a cis-acting regulatory signal for the modulation of neuro can expression in the developing CNS. Neurocan and phosphacan bind sat urably, reversibly, and with high affinity to neural cell adhesion mol ecules (Ng-CAM/L1, NCAM, TAG-1/axonin-1) and to tenascin-C. The proteo glycans and their ligands have overlapping localizations in the CNS, a nd binding of phosphacan to Ng-CAM/L1, NCAM, and tenascin-C is mediate d by complex-type N-linked oligosaccharides on the proteoglycan. Neuro can and phosphacan also bind to neurons and are potent inhibitors of n euronal and glial adhesion and of neurite outgrowth. Through their int eractions with neural cell adhesion and extracellular matrix molecules , these proteoglycans may play a major role in modulating cell adhesio n, neurite growth, and signal transduction across the plasma membrane during the development of the CNS.