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Article
X-PACSIN2 is a regulator of the Metalloprotease/Disintegrin ADAM13
Developmental Biology (2000)
  • Dominique Alfandari, University of Massachusetts - Amherst
  • H. Cousin
  • A. Gaultier
  • C. Bleux
  • T. Darribere
Abstract

ADAM13 is a cell surface metalloprotease expressed in cephalic neural crest cells during early Xenopus development. The cytoplasmic domain of ADAM13 contains three potential SH3 (Src homology type 3) binding sites, suggesting that this region may support interactions with intracellular proteins. In this report we describe the identification, by a new strategy, of three proteins that bind the ADAM13 cytoplasmic domain in vitro: X-Src1, X-An4, and X-PACSIN2. We focused our study on X-PACSIN2 protein because it colocalizes with ADAM13 in migrating neural crest cells during embryonic development. Using pull-down experiments we show that X-PACSIN2 binds to ADAM13 in vitro. Using Xenopus XTC cells, we demonstrate that ADAM13 and X-PACSIN2 colocalize to membrane ruffles and cytoplasmic vesicles. We also show that X-PACSIN2 overexpression can rescue developmental alterations induced by overexpression of ADAM13, suggesting that both proteins interact in vivo. Finally, our results suggest that X-PACSIN2 overexpression reduces endogenous ADAM13 function while a truncated X-PACSIN2 (ΔSH3) increases this activity in cephalic neural crest cells. We propose that X-PACSIN2 may regulate ADAM13 activity by influencing either its subcellular localization or its catalytic activity. In agreement with this model, elimination of the ADAM13 cytoplasmic domain increased developmental alterations attributable to ADAM13 proteolytic activity.

Keywords
  • ADAM,
  • development,
  • PACSIN,
  • SH3,
  • Xenopus,
  • neural crest
Disciplines
Publication Date
November 1, 2000
Publisher Statement
http://dx.doi.org/10.1006/dbio.2000.9871
Citation Information
Dominique Alfandari, H. Cousin, A. Gaultier, C. Bleux, et al.. "X-PACSIN2 is a regulator of the Metalloprotease/Disintegrin ADAM13" Developmental Biology Vol. 227 Iss. 1 (2000)
Available at: http://works.bepress.com/dominique_alfandari/10/