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Updated: Jul 2, 2026

Measuring Transcellular Interactions through Protein Aggregation in a Heterologous Cell System
Published on: May 22, 2020
Neuronal RA175/SynCAM1 isoforms are processed by tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM17-like
Yuko Tanabe1, Tadashi Kasahara, Takashi Momoi
1Division of Development and Differentiation, Department of Human Inherited Metabolic Disease, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi-machi, Kodaira, Tokyo 187-8502, Japan.
Abstract:
RA175/SynCAM1, a member of immunoglobulin superfamily 4 (Igsf4; recently named Cadm1), is a cell adhesion molecule involved in the formation of a functional synapse. Little is known about the modulation of RA175/SynCAM1-mediated synaptic formation and plasticity. Neurons express two major isoforms containing exons 7-8a-8b-9 and exons 7-8b-9. We found that these isoforms were processed within an 11-amino acid sequence, encoded by exon 8b, near the transmembrane domain. TNF-alpha protease inhibitor-1 (TAPI-1) blocked the processing of RA175/SynCAM1 (exons 7-8a-8b-9). Furthermore, TAPI-1 increased the number of synaptophysin and RA175/SynCAM1 colocalization on the dendrites of neurons. Non-cleaved RA175/SynCAM1 was located at the synapse and membrane-bound, cleaved fragments were detected at the non-synaptic region of dendrites. These results suggest that tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM17-like proteases play a role in synaptic formation to generate specific neuronal connections by processing the excess amount of RA175/SynCAM1 located in the non-synaptic region.
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