ABSTRACT
The expression of the sorCS1 protein in the central nervous system of adult mice was studied by immunohistochemistry. A detailed mapping revealed a distribution of sorCS1 immunoreactivity in a widespread population of neurons throughout the brain. Two different types of cellular localization were observed. Many neurons exhibited a punctate cytoplasmic staining which extended into the dendrites, in other neurons sorCS1 immunoreactivity was associated with the plasma membrane. This suggests variable functions for sorCS1 in the neurons of the brain.
Subject(s)
Brain/cytology , Dendrites/chemistry , Membrane Glycoproteins , Membrane Transport Proteins , Neurons/chemistry , Receptors, Cell Surface/analysis , Saccharomyces cerevisiae Proteins , Vesicular Transport Proteins , Animals , Blotting, Western , Cell Membrane/chemistry , Cytoplasm/chemistry , Fungal Proteins/chemistry , Immunohistochemistry , Mice , Mice, Inbred C57BL , Neurons/ultrastructure , Protein Structure, Tertiary , Rabbits , Receptors, Cell Surface/chemistry , Receptors, Cell Surface/immunologyABSTRACT
The two human proteins with a VPS10 domain, SorLA and sortilin, both bind neuropeptides. Searching for other VPS10-domain proteins in the database revealed three new putative human neuropeptide receptors. The new receptors were designated SorCS1, SorCS2 and SorCS3, due to their identical domain composition, which, except for the N-terminal VPS10 domain, differs from that of SorLA and sortilin. Using the databases of the human genome project we elucidated the exon-intron structures of the human VPS10-receptor genes. They contain many short exons, separated by introns, several of which extend over more than 50 kb. The three SorCS genes encompass more than 500 kb of genomic DNA and therefore represent some of the largest known human genes. All these genes map to chromosomal localisations of known genetic diseases, many of them neurological disorders, corresponding to the strong expression of these receptors in the brain. CpG islands are located in the first exon of each of the VPS10-receptor genes and might be involved in developmental or tissue-specific regulation of gene expression.
Subject(s)
Exons/genetics , Receptors, Neuropeptide/genetics , Amino Acid Sequence , Binding Sites , Blotting, Northern , Chromosome Mapping , CpG Islands/genetics , DNA, Complementary/chemistry , DNA, Complementary/genetics , Evolution, Molecular , Genes/genetics , Molecular Sequence Data , Phylogeny , Protein Isoforms/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Tissue DistributionABSTRACT
We report the identification of a fourth member of the VPS10 domain containing receptor family, SorCS2, highly expressed in the developing and mature murine central nervous system. During early central nervous system development its main site of expression is the floor plate. In addition, high transcript levels were detected transiently in a variety of brain regions including the dopaminergic midbrain nuclei and the dorsal thalamus. Outside the nervous system expression is detected in lung and heart and transiently in a variety of mesodermally derived tissues.