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Elife 2017 Aug 22;6. doi: 10.7554/eLife.26898.
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Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a.

Khedgikar V , Abbruzzese G , Mathavan K , Szydlo H , Cousin H , Alfandari D .

Adam13/33 is a cell surface metalloprotease critical for cranial neural crest (CNC) cell migration. It can cleave multiple substrates including itself, fibronectin, ephrinB, cadherin-11, pcdh8 and pcdh8l (this work). Cleavage of cadherin-11 produces an extracellular fragment that promotes CNC migration. In addition, the adam13 cytoplasmic domain is cleaved by gamma secretase, translocates into the nucleus and regulates multiple genes. Here, we show that adam13 interacts with the arid3a/dril1/Bright transcription factor. This interaction promotes a proteolytic cleavage of arid3a and its translocation to the nucleus where it regulates another transcription factor: tfap2α. Tfap2α in turn activates multiple genes including the protocadherin pcdh8l (PCNS). The proteolytic activity of adam13 is critical for the release of arid3a from the plasma membrane while the cytoplasmic domain appears critical for the cleavage of arid3a. In addition to this transcriptional control of pcdh8l, adam13 cleaves pcdh8l generating an extracellular fragment that also regulates cell migration.

PubMed ID: 28829038
PMC ID: PMC5601995
Article link: Elife
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: adam13 adam19 adam9 arid3a ctnnb1 fn1 foxd3 myc pcdh8 pcdh8l prl.1 prl.2 rpn1 smad2 smad7 snai2 tfap2a yy1
Antibodies: Adam13 Ab1 Adam13 Ab3 Adam13 Ab6 Adam13 Ab7 FLAG Ab3 Pcdh8l Ab1 Rpn1 Ab1 Tfap2a Ab1
Morpholinos: adam13 MO3 arid3a MO1 ctnnb1 MO1 foxd3 MO1 pcdh8l MO1 pcdh8l MO2 smad2 MO1 smad2 MO2 tfap2a MO1

Article Images: [+] show captions
References [+] :
Abbruzzese, The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity. 2015, Pubmed, Xenbase