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. 2016 Sep 21;11(9):e0162120.
doi: 10.1371/journal.pone.0162120. eCollection 2016.

Mouse Specific Cleavage-Resistant RAGE Splice Variant

Tohru Fukai  1
Affiliations

Mouse Specific Cleavage-Resistant RAGE Splice Variant

Tohru Fukai. PLoS One. .
No abstract available

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Conflict of interest statement

The author is a member of the PLOS ONE Editorial Board.

Figures

Fig 1
Fig 1. Proposed model of regulation and function of mouse specific cleavage-resistant RAGE Splice Variant mRAGEv4.
RAGE is composed of the ectodomain (ECD)(three Ig domains: V, C1, and C2), juxtra-membrane region including ADAM motif, transmembrane domain, and intracellular domain (ICD). V and C1 domains carry a positive charge, in contrast to the C2 domain, which is negatively charged. Most ligands bind to the V domain of RAGE. RAGE can form soluble RAGE (sRAGE) by two possible mechanisms: the alternative splicing of the transmembrane domain (hRAGEv1, mRAGEv1, mRAGEv3) or the proteolytic cleavage from the cell surface (mRAGE-FL). Either in the baseline (constitutive response) or in the presence of stimuli, ADAM10 will be activated. This cleaves RAGE at the juxtamembrane region, releasing the RAGE ectodomain (ECD), which stimulates or inhibits endosomal signaling and various cellular responses (cell migration, adhesion, etc). The data about mouse-specific mRAGEv4 splice variant presented by Lin’s and Raucci’s group in this article suggests that the peptide motif recognized by ADAM10, which lacks in mRAGEv4, not only renders cleavage of mRAGE-FL by sheddases, but also directs the intracellular cellular trafficking of the full-length receptor.
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