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Dev Biol 2000 Nov 01;2271:197-210. doi: 10.1006/dbio.2000.9871.
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PACSIN2 is a regulator of the metalloprotease/disintegrin ADAM13.

Cousin H , Gaultier A , Bleux C , Darribère T , Alfandari D .

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 (DeltaSH3) 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.

PubMed ID: 11076687
Article link: Dev Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: adam13 adam28.2 fn1 ncoa1 nup93 pacsin2 snai2 src
Antibodies: Adam13 Ab1 Myc Ab5 Pacsin2 Ab1 Src Ab1

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