Neuronal RA175/SynCAM1 isoforms are processed by tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM17-like proteases.
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.
Tanabe
Yuko
Y
Division 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.
Kasahara
Tadashi
T
Momoi
Takashi
T
Fujita
Eriko
E
D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000818:Animals; D019556:COS Cells / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology; D002522:Chlorocebus aethiops; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006877:Hydroxamic Acids / Q000494:pharmacology; D007136:Immunoglobulins; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D016708:Synaptophysin / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
C465040:Cadm1 protein, rat; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D004151:Dipeptides; D006877:Hydroxamic Acids; D007136:Immunoglobulins; C092152:N-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2'-naphthyl)alanylalanine, 2-aminoethylamide; D020033:Protein Isoforms; D016708:Synaptophysin; D025521:Tumor Suppressor Proteins; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse; C000606464:Adam17 protein, rat