Immunoelectron‐microscopic localization of the 180 kD component of the neural cell adhesion molecule N‐CAM in postsynaptic membranes

Abstract

In order to investigate the expression of cell adhesion molecules in synapses, we have studied the localization of the neural cell adhesion molecule N-CAM in the cerebellum and hippocampus of adult mice by immunocytological and immunochemical methods. Of the three molecular components of N-CAM with relative molecular masses (Mr) of 120, 140, and 180 kD, N-CAM 120 is not detectable in synaptosomal membranes, whereas N-CAM 140 is expressed on both pre- and postsynaptic membranes and N-CAM 180 is restricted to postsynaptic sites, with localization of the N-CAM 180-specific epitope in postsynaptic densities. Specificity of immunoreactivity is indicated by the observation that antibodies to the neural cell adhesion molecule L1 do not label synaptic membranes, whereas antibodies to two major components of postsynaptic densities, actin and erythrocyte spectrin, react with synaptic structures. Interestingly, N-CAM 180 is only detectable in subpopulations of synapses in the intact tissue. Isolated synaptosomes, opened for unimpeded accessibility of antibody by hypoosmotic treatment, also reveal a partial expression of N-CAM 180 in that 67% are labeled by antibodies to N-CAM 180, while antibodies to actin and erythrocyte spectrin react with 95% and 88% of all synaptosomes, respectively. N-CAM 180 does not appear to be differentially expressed in synapses of a particular morphological type, but is detectable in all types of synapses in the cerebellum and hippocampus, except for mossy fiber synapses and synapses between basket and Purkinje cells, which are generally N-CAM 180-negative. Since N-CAM 180 has been shown to be characteristic of stabilized or stabilizing cell contacts, possibly by its association with the cytoskeleton-membrane linker protein spectrin (Pollerberg et al.: J. Cell Biol. 101:1921-1929, '85; Nature 324:462-465, '86; Cell Tissue Res. 250:227-236, '87), we would like to suggest N-CAM 180 plays an important role in determining the stability of contacts between pre- and postsynaptic membranes and state of synaptic activity.

Class I histone deacetylase inhibition ameliorates social cognition and cell adhesion molecule plasticity deficits in a rodent model of autism spectrum disorder

“…This deficit not only confirms the observed inability of VPA-treated animals to acquire and consolidate the water maze paradigm (Murphy et al, 1996;Sandi et al, 2004) but may also be relevant to the social approach avoidance abnormalities that are observed in these animals. NCAM-null mice, for example, exhibit social deficits manifested by increased aggression, an effect that is counteracted by the introduction of transgenic NCAM180 (Stork et al, 2000), the synapse-specific isoform that carries PSA in adult animals (Persohn et al, 1989;Doyle et al, 1992). Moreover, mice lacking the polysialyltransferase that regulates NCAM PSA in adulthood (PST or ST8SiaIV) also exhibit social deficits and these become even more severe in mice lacking the developmental enzyme (STX or ST8SiaII) (Calandreau et al, 2010).…”

Conditional Ablation of the Neural Cell Adhesion Molecule Reduces Precision of Spatial Learning, Long-Term Potentiation, and Depression in the CA1 Subfield of Mouse Hippocampus

“…These data suggest that a major portion of residual NCAM expression in the hippocampus is derived from axons projecting to the hippocampus. Furthermore, because NCAM is expressed not only by neurons (Persohn et al, 1989;Prieto et al, 1989) but also by glia (Keilhauer et al, 1985;Noble et al, 1985), and because the ␣CaMKII promoter has not been reported to be active in glia, NCAM expression in the hippocampus may also be attributable to the presence of astrocytes and, less so, oligodendrocytes.…”

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

“…N-CAM is also localized to the motor end plate of the myofibril of striated muscle (16). Within the nervous system, N-CAM-180 is found polarized to growth cones (17), to sites of cell-cell contact (18), and to postsynaptic membranes (19). Additionally, N-CAM-180 is polarized to the somatodendritic domain and excluded from axons of mouse hippocampal neurons (20).…”