Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28154010
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biol+Chem
2017 ; 292
(10
): 4210-4221
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Extracellular Loops Are Essential for the Assembly and Function of Polycystin
Receptor-Ion Channel Complexes
#MMPMID28154010
Salehi-Najafabadi Z
; Li B
; Valentino V
; Ng C
; Martin H
; Yu Y
; Wang Z
; Kashyap P
; Yu Y
J Biol Chem
2017[Mar]; 292
(10
): 4210-4221
PMID28154010
show ga
Polycystin complexes, or TRPP-PKD complexes, made of transient receptor potential
channel polycystin (TRPP) and polycystic kidney disease (PKD) proteins, play key
roles in coupling extracellular stimuli with intracellular Ca(2+) signals. For
example, the TRPP2-PKD1 complex has a crucial function in renal physiology, with
mutations in either protein causing autosomal dominant polycystic kidney disease.
In contrast, the TRPP3-PKD1L3 complex responds to low pH and was proposed to be a
sour taste receptor candidate. It has been shown previously that the protein
partners interact via association of the C-terminal or transmembrane segments,
with consequences for the assembly, surface expression, and function of the
polycystin complexes. However, the roles of extracellular components, especially
the loops that connect the transmembrane segments, in the assembly and function
of the polycystin complex are largely unknown. Here, with an immunoprecipitation
method, we found that extracellular loops between the first and second
transmembrane segments of TRPP2 and TRPP3 associate with the extracellular loops
between the sixth and seventh transmembrane segments of PKD1 and PKD1L3,
respectively. Immunofluorescence and electrophysiology data further confirm that
the associations between these loops are essential for the trafficking and
function of the complexes. Interestingly, most of the extracellular loops are
also found to be involved in homomeric assembly. Furthermore, autosomal dominant
polycystic kidney disease-associated TRPP2 mutant T448K significantly weakened
TRPP2 homomeric assembly but had no obvious effect on TRPP2-PKD1 heteromeric
assembly. Our results demonstrate a crucial role of these functionally
underexplored extracellular loops in the assembly and function of the polycystin
complexes.