title: Translocation of the cytoplasmic domain of ADAM13 to the nucleus is essential for Calpain8-a expression and cranial neural crest cell migration.
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.
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA. hcousin@vasci.umass.edu
authors.forename: Hélène
authors.initials: H
authors.lastname: Cousin
authors.forename: Genevieve
authors.initials: G
authors.lastname: Abbruzzese
authors.forename: Erin
authors.initials: E
authors.lastname: Kerdavid
authors.forename: Alban
authors.initials: A
authors.lastname: Gaultier
authors.forename: Dominique
authors.initials: D
authors.lastname: Alfandari
mesh_terms: D051722:ADAM Proteins / Q000737:chemistry* / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D002154:Calpain / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism*; D017124:Conserved Sequence / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012886:Skull / Q000166:cytology*; D013329:Structure-Activity Relationship; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D029867:Xenopus Proteins; D053829:Amyloid Precursor Protein Secretases; C557048:CAPN8 protein, Xenopus; D002154:Calpain; D051722:ADAM Proteins; C539706:ADAM19 protein, Xenopus; C104937:ADAM33 protein, Xenopus