PKHD1 protein encoded by the gene for autosomal recessive polycystic kidney disease associates with basal bodies and primary cilia in renal epithelial cells.
Mutations of the polycystic kidney and hepatic disease 1 (PKHD1) gene have been shown to cause autosomal recessive polycystic kidney disease (ARPKD), but the cellular functions of the gene product (PKHD1) remain uncharacterized. To illuminate its properties, the spatial and temporal expression patterns of PKHD1 were determined in mouse, rat, and human tissues by using polyclonal Abs and mAbs recognizing various specific regions of the gene product. During embryogenesis, PKHD1 is widely expressed in epithelial derivatives, including neural tubules, gut, pulmonary bronchi, and hepatic cells. In the kidneys of the pck rats, the rat model of which is genetically homologous to human ARPKD, the level of PKHD1 was significantly reduced but not completely absent. In cultured renal cells, the PKHD1 gene product colocalized with polycystin-2, the gene product of autosomal dominant polycystic disease type 2, at the basal bodies of primary cilia. Immunoreactive PKHD1 localized predominantly at the apical domain of polarized epithelial cells, suggesting it may be involved in the tubulogenesis and/or maintenance of duct-lumen architecture. Reduced PKHD1 levels in pck rat kidneys and its colocalization with polycystins may underlie the pathogenic basis for cystogenesis in polycystic kidney diseases.
Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA.
Ming-Zhi
MZ
Zhang
Weiyi
W
Mai
Cunxi
C
Li
Sae-youll
SY
Cho
Chuanming
C
Hao
Gilbert
G
Moeckel
Runxiang
R
Zhao
Ingyu
I
Kim
Jikui
J
Wang
Huaqi
H
Xiong
Hong
H
Wang
Yasunori
Y
Sato
Yizhong
Y
Wu
Yasuni
Y
Nakanuma
Marusia
M
Lilova
York
Y
Pei
Raymond C
RC
Harris
Song
S
Li
Robert J
RJ
Coffey
Le
L
Sun
Dianqing
D
Wu
Xing-Zhen
XZ
Chen
Matthew D
MD
Breyer
Zhizhuang Joe
ZJ
Zhao
James A
JA
McKanna
Guanqing
G
Wu
D000328:Adult; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D017931:DNA Primers; D005333:Fetus; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology*; D051379:Mice; D007690:Polycystic Kidney Diseases / Q000201:enzymology / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014158:Transcription, Genetic
D017931:DNA Primers; C451750:PKHD1 protein, human; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins