Translocation of the cytoplasmic domain of ADAM13 to the nucleus is essential for Calpain8-a expression and cranial neural crest cell migration.

TitleTranslocation of the cytoplasmic domain of ADAM13 to the nucleus is essential for Calpain8-a expression and cranial neural crest cell migration.
Publication TypeJournal Article
Year of Publication2011
AuthorsCousin, H, Abbruzzese, G, Kerdavid, E, Gaultier, A, Alfandari, D
JournalDevelopmental cell
Volume20
Issue2
Pagination256-63
Date Published2011 Feb 15
KeywordsADAM Proteins, Amyloid Precursor Protein Secretases, Animals, Calpain, Cell Line, Cell Movement, Cell Nucleus, Conserved Sequence, Embryo, Nonmammalian, Evolution, Molecular, Gene Expression Regulation, Developmental, Humans, Membrane Proteins, Neural Crest, Protein Structure, Tertiary, Protein Transport, Skull, Structure-Activity Relationship, Xenopus laevis, Xenopus Proteins
Abstract

ADAMs are transmembrane metalloproteases that control cell behavior by cleaving both cell adhesion and signaling molecules. The cytoplasmic domain of ADAMs can regulate the proteolytic activity by controlling the subcellular localization and/or the activation of the protease domain. Here, we show that the cytoplasmic domain of ADAM13 is cleaved and translocates into the nucleus. Preventing this translocation renders the protein incapable of promoting cranial neural crest (CNC) cell migration in vivo, without affecting its proteolytic activity. In addition, the cytoplasmic domain of ADAM13 regulates the expression of multiple genes in CNC, including the protease Calpain8-a. Restoring the expression of Calpain8-a is sufficient to rescue CNC migration in the absence of the ADAM13 cytoplasmic domain. This study shows that the cytoplasmic domain of ADAM metalloproteases can perform essential functions in the nucleus of cells and may contribute substantially to the overall function of the protein.

Alternate JournalDev. Cell