Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P41181 (
collecting duct
)
5,183
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We previously demonstrated a role for the myristoylated alanine-rich C kinase substrate (MARCKS) to serve as an adaptor protein in the anionic phospholipid phosphate-dependent regulation of the epithelial sodium channel (ENaC). Both MARCKS and ENaC are regulated by proteolysis. Calpains are a family of ubiquitously expressed intracellular Ca
2+
-dependent cysteine proteases involved in signal transduction. Here we examine the role of
calpain-2
in regulating MARCKS and ENaC in cultured renal epithelial cells and in the mouse kidney. Using recombinant fusion proteins, we show that MARCKS, but not the ENaC subunits, are a substrate of
calpain-2
in the presence of Ca
2+
Pharmacological inhibition of
calpain-2
alters MARCKS protein expression in light-density sucrose gradient fractions from cell lysates of mouse cortical
collecting duct
cells. Calpain-dependent cleaved products of MARCKS are detectable in cultured renal cells. Ca
2+
mobilization and
calpain-2
inhibition decrease the association between ENaC and MARCKS. The inhibition of
calpain-2
reduces ENaC activity as demonstrated by single-channel patch-clamp recordings and transepithelial current measurements. These results suggest that
calpain-2
proteolysis of MARCKS promotes its interaction with lipids and ENaC at the plasma membrane to allow for the phosphatidylinositol 4,5-bisphosphate (PIP2)-dependent regulation of ENaC activity in the kidney.
...
PMID:ENaC activity is regulated by calpain-2 proteolysis of MARCKS proteins. 2846 44
