scholarly journals Revisiting the NaCl cotransporter regulation by with-no-lysine kinases

2015 ◽  
Vol 308 (10) ◽  
pp. C779-C791 ◽  
Author(s):  
Silvana Bazúa-Valenti ◽  
Gerardo Gamba
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Type Ii ◽  
Complex Issue ◽  
Dark Ages ◽  
Ubiquitin Ligase Complex ◽  
Pseudohypoaldosteronism Type Ii ◽  
Cullin 3 ◽  
Increased Activity ◽  
Pseudohypoaldosteronism Type

The renal thiazide-sensitive Na+-Cl− cotransporter (NCC) is the salt transporter in the distal convoluted tubule. Its activity is fundamental for defining blood pressure levels. Decreased NCC activity is associated with salt-remediable arterial hypotension with hypokalemia (Gitelman disease), while increased activity results in salt-sensitive arterial hypertension with hyperkalemia (pseudohypoaldosteronism type II; PHAII). The discovery of four different genes causing PHAII revealed a complex multiprotein system that regulates the activity of NCC. Two genes encode for with-no-lysine (K) kinases WNK1 and WNK4, while two encode for kelch-like 3 (KLHL3) and cullin 3 (CUL3) proteins that form a RING type E3 ubiquitin ligase complex. Extensive research has shown that WNK1 and WNK4 are the targets for the KLHL3-CUL3 complex and that WNKs modulate the activity of NCC by means of intermediary Ste20-type kinases known as SPAK or OSR1. The understanding of the effect of WNKs on NCC is a complex issue, but recent evidence discussed in this review suggests that we could be reaching the end of the dark ages regarding this matter.

scholarly journals Generation and analysis of knock-in mice carrying pseudohypoaldosteronism type II-causing mutations in the cullin 3 gene

Biology Open ◽  
2015 ◽  
Vol 4 (11) ◽  
pp. 1509-1517 ◽  
Author(s):  
Y. Araki ◽  
T. Rai ◽  
E. Sohara ◽  
T. Mori ◽  
Y. Inoue ◽  
...  
Keyword(s):  
Type Ii ◽  
Pseudohypoaldosteronism Type Ii ◽  
Cullin 3 ◽  
Pseudohypoaldosteronism Type

scholarly journals A novel mutation in exon 9 of Cullin 3 gene contributes to aberrant splicing in pseudohypoaldosteronism type II

FEBS Open Bio ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 461-469 ◽  
Author(s):  
Leping Shao ◽  
Li Cui ◽  
Jingru Lu ◽  
Yanhua Lang ◽  
Irene Bottillo ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Type Ii ◽  
Aberrant Splicing ◽  
Pseudohypoaldosteronism Type Ii ◽  
Cullin 3 ◽  
Exon 9 ◽  
Pseudohypoaldosteronism Type

scholarly journals Cross-species analysis of LZTR1 loss-of-function mutants demonstrates dependency to RIT1 orthologs

2022 ◽  
Author(s):  
Antonio Cuevas-Navarro ◽  
Laura Rodriguez-Muñoz ◽  
Joaquim Grego-Bessa ◽  
Alice Cheng ◽  
Katherine A Rauen ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Null Allele ◽  
E3 Ubiquitin Ligase ◽  
Adaptor Protein ◽  
Loss Of Function ◽  
Ras Gtpases ◽  
Ubiquitin Ligase Complex ◽  
Species Analysis ◽  
Cullin 3 ◽  
Ring E3

RAS GTPases are highly conserved proteins involved in the regulation of mitogenic signaling. We have previously described a novel Cullin 3 RING E3 ubiquitin ligase complex formed by the substrate adaptor protein LZTR1 that binds, ubiquitinates, and promotes proteasomal degradation of the RAS GTPase RIT1. In addition, others have described that this complex is also responsible for the ubiquitination of canonical RAS GTPases. Here, we have analyzed the phenotypes of LZTR1 loss-of-function mutants in both fruit flies and mice and have demonstrated biochemical dependency on their RIT1 orthologs. Moreover, we show that LZTR1 is haplosufficient in mice and that embryonic lethality of the homozygous null allele can be rescued by deletion of RIT1.

scholarly journals A young child with pseudohypoaldosteronism type II by a mutation of Cullin 3

2013 ◽  
Vol 14 (1) ◽  
Author(s):  
Shoji Tsuji ◽  
Miyoko Yamashita ◽  
Gen Unishi ◽  
Reiko Takewa ◽  
Takahisa Kimata ◽  
...  
Keyword(s):  
Young Child ◽  
Type Ii ◽  
Pseudohypoaldosteronism Type Ii ◽  
Cullin 3 ◽  
Pseudohypoaldosteronism Type

Familial cases of pseudohypoaldosteronism type II harboring a novel mutation in the Cullin 3 gene

Nephrology ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 818-821
Author(s):  
Kiyoshi Nakano ◽  
Yasuo Kubota ◽  
Takayuki Mori ◽  
Motoko Chiga ◽  
Takayasu Mori ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Type Ii ◽  
Familial Cases ◽  
Pseudohypoaldosteronism Type Ii ◽  
Cullin 3 ◽  
Pseudohypoaldosteronism Type

Decreased KLHL3 expression is involved in the pathogenesis of pseudohypoaldosteronism type II caused by cullin 3 mutation in vivo

2018 ◽  
Vol 22 (6) ◽  
pp. 1251-1257 ◽  
Author(s):  
Sayaka Yoshida ◽  
Yuya Araki ◽  
Takayasu Mori ◽  
Emi Sasaki ◽  
Yuri Kasagi ◽  
...  
Keyword(s):  
Type Ii ◽  
Pseudohypoaldosteronism Type Ii ◽  
Cullin 3 ◽  
Pseudohypoaldosteronism Type

scholarly journals An intracellular pathogen response pathway promotes proteostasis in C. elegans

2017 ◽  
Author(s):  
Kirthi C. Reddy ◽  
Tal Dror ◽  
Jessica N. Sowa ◽  
Johan Panek ◽  
Kevin Chen ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Intracellular Pathogen ◽  
Forward Genetic Screen ◽  
C Elegans ◽  
Transcriptional Signature ◽  
Proteotoxic Stress ◽  
Ubiquitin Ligase Complex ◽  
Pathogen Response ◽  
Mutant Phenotypes ◽  
Increased Activity

SummaryMaintenance of proteostasis is critical for organismal health. Here we describe a novel pathway that promotes proteostasis, identified through the analysis of C. elegans genes upregulated by intracellular infection. We named this distinct transcriptional signature the Intracellular Pathogen Response (IPR), and it includes upregulation of several predicted ubiquitin ligase complex components such as the cullin cul-6. Through a forward genetic screen we found pals-22, a gene of previously unknown function, to be a repressor of the cul-6/Cullin gene and other IPR gene expression. Interestingly, pals-22 mutants have increased thermotolerance and reduced levels of stress-induced polyglutamine aggregates, likely due to upregulated IPR expression. We found the enhanced stress resistance of pals-22 mutants to be dependent on cul-6, suggesting that pals-22 mutants have increased activity of a CUL-6/Cullin-containing ubiquitin ligase complex. pals-22 mutant phenotypes are distinct from the well-studied heat shock and insulin signaling pathways, indicating that the IPR is a novel pathway that protects animals from proteotoxic stress.

scholarly journals A New Locus on Chromosome 12p13.3 for Pseudohypoaldosteronism Type II, an Autosomal Dominant Form of Hypertension

2000 ◽  
Vol 67 (2) ◽  
pp. 302-310 ◽  
Author(s):  
Sandra Disse-Nicodème ◽  
Jean-Michel Achard ◽  
Isabelle Desitter ◽  
Anne-Marie Houot ◽  
Albert Fournier ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Type Ii ◽  
Dominant Form ◽  
Pseudohypoaldosteronism Type Ii ◽  
Autosomal Dominant Form ◽  
Pseudohypoaldosteronism Type
Sign in / Sign up

Export Citation Format

Share Document