Cell surface modulation of the neural cell adhesion molecule resulting from alternative mRNA splicing in a tissue-specific developmental sequence.

Abstract

Abstract. The neural cell adhesion molecule N-CAM is an intrinsic membrane glycoprotein that is expressed in the embryonic chicken nervous system as two different polypeptide chains encoded by alternatively spliced transcripts of a single gene. Because they differ by the presence or absence of ~250 amino acids in their cytoplasmic domains, these polypeptides are designated ld and sd, for large and small cytoplasmic domain, respectively. We report here that the ld-specific sequences comprise a single exon in the chicken N-CAM gene and that developmental expression of the ld and sd chains occurs in a tissue-specific fashion, with the ld chain restricted to the nervous system. Comparison of the nucleotide sequences from an N-CAM genomic clone with cDNA sequences showed that a single exon of 783 base pairs corresponded to the unique cytoplasmic domain of the ld polypeptide. Sequences from this exon were absent from the single N-CAM mRNA detected in several non-neural tissues by RNA blot hybridization, and immunoblot analysis confirmed that antigenic determinants unique to the ldspecific domain were not expressed in these tissues. Immunohistochemical experiments indicated that only the sd chain was expressed on cell surfaces of nonneural tissues throughout embryonic development. The ld chain was found on cell bodies and neurites of differentiated neurons; it first appeared as neurons began to extend neurites and to express the neuron-glia cell adhesion molecule (Ng-CAM) and it was restricted to definite layers in laminar tissues such as the retina and cerebellum. These results suggest that the control of mRNA splicing may affect the regulation of N-CAM function at specific sites within the nervous system and thus influence the control of neural morphogenesis and histogenesis.

The Neural Cell Adhesion Molecule Expresses a Tyrosine-independent Basolateral Sorting Signal

“…N-CAM has since been found to be developmentally expressed as a family of isoforms in a variety of both neural and non-neural tissues including skin (3), muscle (4), and liver (5). N-CAM mediates cellular adhesion through both homophilic (6) and heterophilic contacts (7,8) and is capable of activating intracellular secondary messenger systems (9,10).…”

Neural cell adhesion molecules in rat endocrine tissues and tumor cells: distribution and molecular analysis.

“…Exon 15 codes for the membrane anchoring sequence of NCAM-120 as well as for the NCAM-120-specific 3'-noncoding region. Exons 16,17, and 19 characterize both NCAM-140 and -180, whereas exon 18 codes for an additional cytoplasmic insert unique to NCAM-180 (9)(10)(11)(12).…”

A short segment within the cytoplasmic domain of the neural cell adhesion molecule (N-CAM) is essential for N-CAM-induced NF-κB activity in astrocytes

“…Like the sd N-CAM, ld N-CAM is phosphorylated on multiple threonine and serine residues, although to different extents and at different sites than in the sd N-CAM (38). Because the ld isoform is present only in neurons and not in other adult tissues that express N-CAM, such as skeletal muscle (14), it is possible that the differential phosphorylation of the sd and ld isoforms may be related to specific interactions with proteins in different signaling pathways, whereas the phosphorylation of sites in common to both isoforms may represent overlapping functions. Furthermore, the glycosylphosphatidylinositol-linked ssd N-CAM may be a potential signaling receptor for N-CAM binding.…”

“…This protein has a number of differentially spliced forms, including two transmembrane forms (sd and ld) and a glycosylphosphatidylinositol-linked form (ssd) (10,11). After translation, N-CAM molecules can be modified in a number of ways, including N-linked polysialylation (12), phosphorylation on multiple intracellular serine and threonine residues (13), and palmitoylation of cytosolic cysteines (14,15).…”