Enhanced Nerve–Mast Cell Interaction by a Neuronal Short Isoform of Cell Adhesion Molecule-1

Abstract

Close apposition of nerve and mast cells is viewed as a functional unit of neuro-immune mechanisms, and it is sustained by trans-homophilic binding of cell adhesion molecule-1 (CADM1), an Ig superfamily member. Cerebral nerve–mast cell interaction might be developmentally modulated, because the alternative splicing pattern of four (a–d) types of CADM1 transcripts drastically changed during development of the mouse cerebrum: developing cerebrums expressed CADM1b and CADM1c exclusively, while mature cerebrums expressed CADM1d additionally and predominantly. To probe how individual isoforms are involved in nerve–mast cell interaction, Neuro2a neuroblastoma cells that express CADM1c endogenously were modified to express additionally either CADM1b (Neuro2a-CADM1b) or CADM1d (Neuro2a-CADM1d), and they were cocultured with mouse bone marrow-derived mast cells (BMMCs) and BMMC-derived cell line IC-2 cells, both of which expressed CADM1c. BMMCs were found to adhere to Neuro2a-CADM1d neurites more firmly than to Neuro2a-CADM1b neurites when the adhesive strengths were estimated from the femtosecond laser-induced impulsive forces minimally required for detaching BMMCs. GFP-tagging and crosslinking experiments revealed that the firmer adhesion site consisted of an assembly of CADM1d cis-homodimers. When Neuro2a cells were specifically activated by histamine, intracellular Ca2+ concentration was increased in 63 and 38% of CADM1c-expressing IC-2 cells that attached to the CADM1d assembly site and elsewhere, respectively. These results indicate that CADM1d is a specific neuronal isoform that enhances nerve–mast cell interaction, and they suggest that nerve–mast cell interaction may be reinforced as the brain grows mature because CADM1d becomes predominant.

Time-Course Statistical Evaluation of Intercellular Adhesion Maturation by Femtosecond Laser Impulse

“…Hagiyama et al reported that the frequency of signal-transduction detection was~40% in their study (36). This percentage was similar to that of the cells indicating the higher breaking force (0.8 Â 10 À12 Ns), which is estimated to be 30-40% (Fig.…”

“…In a previous study, our group evaluated the adhesion behavior between neuroblastoma cells (neuro2a) and mast cells, in which several isoforms of CADM1 were expressed exogenously (36). The results indicated that the spatial distribution of CADM1s on the neurite differed among the isoforms, resulting in different adhesion strengths.…”

Polysialylation of the Synaptic Cell Adhesion Molecule 1 (SynCAM 1) Depends Exclusively on the Polysialyltransferase ST8SiaII in Vivo

“…However, based on RT-PCR and sequencing of the obtained products, we demonstrated the occurrence of three exon 8c-containing transcript variants (i.e. 8abc, 8bc, and 8c), which were not identified in similar approaches performed previously to study developmental changes in the Syn-CAM 1 transcript pattern in the mouse brain (10,11).…”

“…IP, immunoprecipitation; WB, Western blot analysis. Notably, transcript variant 8abc showed a constantly low expression level throughout postnatal brain development, which might have hampered the identification of this variant in previous studies (10,11). Transcript variant 8c was hardly detectable before P7/P9 but was constantly expressed thereafter.…”

“…In the case of human SynCAM 1, differential usage of three alternative exons, here termed exons 8a, 8b, and 8c, can theoretically lead to eight membrane-bound isoforms, which differ only in a short juxtamembranous extracellular stem region. In mice, however, the variable exon 8c has been described as cryp-* This work was supported by Deutsche Forschungsgemeinschaft Grants GE tic exon, and expression has been reported only for transcript variants lacking this exon (8,10,11). Notably, the peptide sequences encoded by the variable exons contain a high number of potential O-glycosylation sites (8), and developmental changes in SynCAM 1 glycosylation that are unique among synaptic adhesion molecules have been observed (12).…”