Annexin A5 interacts with polycystin-1 and interferes with the polycystin-1 stimulated recruitment of E-cadherin into adherens junctions.
Polycystin-1 is the gene product of PKD1, the first gene identified to be causative for the condition of autosomal dominant polycystic kidney disease (ADPKD). Mutations in PKD1 are responsible for the majority of ADPKD cases worldwide. Polycystin-1 is a protein of the transient receptor potential channels superfamily, with 11 transmembrane spans and an extracellular N-terminal region of approximately 3109 amino acid residues, harboring multiple putative ligand binding domains. We demonstrate here that annexin A5 (ANXA5), a Ca(2+) and phospholipid binding protein, interacts with the N-terminal leucine-rich repeats of polycystin-1, in vitro and in a cell culture model. This interaction is direct and specific and involves a conserved sequence of the ANXA5 N-terminal domain. Using Madin-Darby canine kidney cells expressing polycystin-1 in an inducible manner we also show that polycystin-1 colocalizes with E-cadherin at cell-cell contacts and accelerates the recruitment of intracellular E-cadherin to reforming junctions. This polycystin-1 stimulated recruitment is significantly delayed by extracellular annexin A5.
Markoff
Arseni
A
Institute of Medical Biochemistry, Westfalian-Wilhelms University of Muenster, Von Esmarch Str. 56, 48149 Muenster, Germany. markoff@uni-muenster.de <markoff@uni-muenster.de>
Bogdanova
Nadia
N
Knop
Markus
M
Rüffer
Claas
C
Kenis
Heidi
H
Lux
Petra
P
Reutelingsperger
Chris
C
Todorov
Vassil
V
Dworniczak
Bernd
B
Horst
Jürgen
J
Gerke
Volker
V
D022005:Adherens Junctions / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D017304:Annexin A5 / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003432:Cross-Linking Reagents; D004285:Dogs; D006801:Humans; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D050396:TRPP Cation Channels / Q000378:metabolism*
D017304:Annexin A5; D015820:Cadherins; D003432:Cross-Linking Reagents; D010455:Peptides; D050396:TRPP Cation Channels