Fibrocystin interacts with CAML, a protein involved in Ca2+ signaling.
The predicted structure of the autosomal recessive polycystic kidney disease protein, fibrocystin, suggests that it may function as a receptor, but its function remains unknown. To understand its function, we searched for proteins that interact with the intracellular C-terminus of fibrocystin using the yeast two-hybrid system. From the screening, we found calcium modulating cyclophilin ligand (CAML), a protein involved in Ca(2+) signaling. Immunofluorescent analysis showed that both proteins are co-localized in the apical membrane, primary cilia, and the basal body of cells derived from the distal nephron Epitope-tagged expression constructs of both proteins were co-immunoprecipitated from COS7 cells. The intracellular C-terminus of fibrocystin interacts with CAML, a protein with an intracellular distribution that is similar to that of PKD2. Fibrocystin may participate in regulation of intracellular Ca(2+) in the distal nephron in a manner similar to PKD1 and PKD2 that are involved in autosomal dominant polycystic kidney disease.
Nagano
Junko
J
Division of Nephrology, Department of Medicine, Case Western Reserve University, Lois Stokes Veterans Affairs Medical Center, Cleveland, OH, USA.
Kitamura
Kenichiro
K
Hujer
Kristine M
KM
Ward
Christopher J
CJ
Bram
Richard J
RJ
Hopfer
Ulrich
U
Tomita
Kimio
K
Huang
Chunfa
C
Miller
R Tyler
RT
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002522:Chlorocebus aethiops; D006801:Humans; D007690:Polycystic Kidney Diseases / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C089404:CAMLG protein, human; C451750:PKHD1 protein, human; D011956:Receptors, Cell Surface; D002118:Calcium