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Journal of Neuroscience, Vol 13, 195-207, Copyright © 1993 by Society for Neuroscience
A large chondroitin sulfate proteoglycan has the characteristics of a general extracellular matrix component of adult brain
M Iwata and SS Carlson
Department of Physiology and Biophysics, University of Washington, Seattle 98195.
Extracellular matrix (ECM) is a secreted extracellular network. Few
components of adult brain ECM are known. We have identified a new, large
chondroitin sulfate proteoglycan (T1 antigen) that acts like a general ECM
protein of brain. First, it is present throughout the brain; second, it has
the properties of an extracellular protein; and third, it is extracted only
under denaturing conditions. Immunocytochemical localization of the T1
antigen by light microscope shows it to be present throughout the rat brain
in both white and gray matter. The T1 antigen outlines Purkinje and other
large cells. No antigenicity is seen inside these cells. Biochemical
evidence suggests that the T1 antigen is extracellular rather than
cytosolic or intravesicular. The T1 antigen is disulfide-linked to two
other proteins. Disulfide bonds are found only in extracellular or
intravesicular proteins, not in intracellular cytosolic proteins. Moreover,
the T1 antigen is probably not intravesicular. Unlike intravesicular
proteins, only a small amount of T1 antigen is solubilized by nondenaturing
detergents. While nondenaturing detergents extract but a small amount of T1
antigen from rat brain, the majority is solubilized by denaturing
conditions (6 M guanidine-HCl). This behavior is similar to that of ECM
components in other tissues and is unlike that of membrane proteins, even
those linked to the cytoskeleton. We hypothesize that the insolubility of
the T1 antigen in brain is due to its presence in an extracellular
aggregate. The T1 antigen is a proteoglycan with a highly glycosylated
protein core of 300 kDa. It does not appear to be related to the large,
heavily glycosylated chondroitin sulfate proteoglycans aggrecan and
versican, which were discovered in non-neural tissues. Antibodies to a 15
residue peptide present in both aggrecan and versican do not react with the
T1 antigen.
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