Neural Cell Adhesion Molecule: Structure, Immunoglobulin-Like Domains, Cell Surface Modulation, and Alternative RNA Splicing

Abstract

The neural cell adhesion molecule, N-CAM, appears on early embryonic cells and is important in the formation of cell collectives and their boundaries at sites of morphogenesis. Later in development it is found on various differentiated tissues and is a major CAM mediating adhesion among neurons and between neurons and muscle. To provide a molecular basis for understanding N-CAM function, the complete amino acid sequences of the three major polypeptides of N-CAM and most of the noncoding sequences of their messenger RNA's were determined from the analysis of complementary DNA clones and were verified by amino acid sequences of selected CNBr fragments and proteolytic fragments. The extracellular region of each N-CAM polypeptide includes five contiguous segments that are homologous in sequence to each other and to members of the immunoglobulin superfamily, suggesting that interactions among immunoglobulin-like domains form the basis for N-CAM homophilic binding. Although different in their membrane-associated and cytoplasmic domains, the amino acid sequences of the three polypeptides appear to be identical throughout this extracellular region (682 amino acids) where the binding site is located. Variations in N-CAM activity thus do not occur by changes in the amino acid sequence that alter the specificity of binding. Instead, regulation is achieved by cell surface modulation events that alter N-CAM affinity, prevalence, mobility, and distribution on the surface. A major mechanism for modulation is alternative RNA splicing resulting in N-CAM's with different cytoplasmic domains that differentially interact with the cell membrane. Such regulatory mechanisms may link N-CAM binding function with other primary cellular processes during the embryonic development of pattern.

Cloning, expression and chromosomal localization of a new putative receptor‐like protein tyrosine phosphatase

“…The extracellular region of RPTPp contains one Iglike domain and 4 fibronectin (FN) type Ill-like domains. These structural motifs have previously been identified in EAR, HPTP/I, HPTPG and in several other cell-surface molecules, such as the cell-adhesion molecule N-CAM [42] and the product of the tumor suppressor gene, DCC 1431, In addition to these motifs, the Nterminus of the predicted RPTP,u protein contains a stretch of 170 amino acids (residues 2 I-196) that shows no significant similarity to known sequences in the EIMBE and GenBank databases. The deduced structure of the RPTP@ protein, as compared to that of several related RPTPs, is schematically shown in Fig.…”

A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors

“…AXL transduces signals from the ECM into the cytoplasm by binding to GAS-6 a g-carboxylated secreted protein that is sixfold overexpressed in GIST-R and is involved in the stimulation of cell proliferation by binding and activating AXL through an autocrine mechanism. This receptor can also mediate cell aggregation by homophilic binding (Cunningham et al, 1987). c-Met, overexpressed and activated in numerous human carcinomas, binds to HGF which is 14-fold overexpressed in GIST-R cells and activates signaling in an autocrine manner (Michieli et al, 2004).…”

Aberrant expression of epithelial and neuroendocrine markers in alveolar rhabdomyosarcoma: a potentially serious diagnostic pitfall

“…Not all cases contained sufficient tissue for all studies; overall wide-spectrum cytokeratin was performed in 44 cases, low molecular weight cytokeratin in 27 cases, synaptophysin in 37 cases, chromogranin A in 36 (45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60) years old), and two older adults 460 years of age. The primary tumors were available for study in 36 cases; for eight patients only metastases (seven to lymph nodes, one to lung) were available.…”

“…56,57 CD56 is expressed by many normal cells and tissues, including neurons, astrocytes and glia, adrenal cortex and medulla, renal proximal tubules, follicular epithelium of the thyroid, gastric parietal cells, cardiac muscle, regenerating and fetal skeletal muscle, pancreatic islet cells, human natural killer cells, a subset of T lymphocytes and peripheral nerve. [58][59][60] CD56 may be expressed by a variety of sarcomas, including synovial sarcoma, malignant peripheral nerve sheath tumor, leiomyosarcoma, chondrosarcoma, and osteosarcoma.…”