Developmental Regulation of LR11 Expression in Murine Brain

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Abstract
Receptors belonging to the low density lipoprotein receptor (LDLR) superfamily play important biological roles in addition to mediating lipoprotein metabolism. The recent discovery of a novel mosaic LDLR family member by us (Yamazaki H., Bujo, H., Kusunoki, J., Seimiya, K., Kanaki, T., Morisaki, N., Schneider, W.J., and Saito, Y. (1996) J. Biol. Chem. 271, 24761-24768) and others, which we termed LR11, offers the opportunity to gain new insights into receptor multifunctionality. The predominant expression of LR11 in brain and the presence of elements found in neural adhesion molecules suggested a function(s) in the central nervous system (CNS). In order to gain information about this complex receptor in an accessible system, we have molecularly characterized the murine LR11 and report on its detailed localization and developmental expression pattern. The primary sequence of the murine protein further establishes that LR11s are among the closest relatives within the LDLR family and that brain is the predominant site of expression. In situ hybridization showed that neuronal bodies such as Purkinje cells in the cerebellum and other neurons in the hippocampal formations and the cerebral cortex are particularly rich in LR11 transcripts. The developmental pattern of LR11 expression in brain, which peaks at 2 weeks, is in contrast to those of two other LDLR family members, the very low density lipoprotein receptor and the LDLR. During early development, murine LR11 expression levels are highly dependent on neural cell types. These findings are compatible with function(s) of LR11 in neural organization and, possibly, pathogenesis of degenerative brain diseases. In addition, detailed knowledge of LR11 biology will help to elucidate the roles of other mosaic proteins that share with LR11 elements whose function is not yet known.