Neuronal RA175/SynCAM1 isoforms are processed by tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM17-like proteases

Neuroscience Letters
Yuko TanabeEriko Fujita

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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Citations

Mar 23, 2012·Cellular and Molecular Life Sciences : CMLS·Elena P MoiseevaPeter Bradding
Nov 19, 2010·The Journal of Biological Chemistry·Nathalie BotPatrick C Fraering
Oct 30, 2008·Biochemical and Biophysical Research Communications·Yu ZhilingMariko Y Momoi
Sep 8, 2011·Stem Cells·Miodrag Stojkovic, Majlinda Lako
Mar 19, 2013·Cell Biology International·Yuko TanabeTakashi Momoi
Dec 27, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Serena QuartaMichaela Kress
Feb 27, 2010·Critical Reviews in Biochemistry and Molecular Biology·Monika Gooz
Apr 13, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Man HagiyamaAkihiko Ito
Jul 15, 2017·Biochimica Et Biophysica Acta. Molecular Cell Research·Friederike Zunke, Stefan Rose-John

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