NHERF-CFTR Complexes in Autosomal Dominant Polycystic Kidney Disease Lecture Notes

Vocabulary flashcards covering the molecular mechanisms of CFTR and NHERF scaffolding interactions in ADPKD based on the provided lecture transcript.

Autosomal dominant polycystic kidney disease (ADPKD)

A condition characterized by progressive cyst growth driven by dysregulated epithelial proliferation, sustained fluid secretion, and aberrant cAMP signaling at apical membranes.

Cystic fibrosis transmembrane conductance regulator (CFTR)

A cAMP-activated chloride channel expressed at the apical membrane of cyst-lining epithelia that serves as a key mediator of cyst fluid accumulation in ADPKD.

Na+/H+ exchanger regulatory factor (NHERF)

PDZ domain–containing scaffolding proteins that regulate CFTR function and localization by integrating ion transport with cytoskeletal organization and signaling pathways.

VX-809 (Lumacaftor)

A CFTR corrector that can reverse pathological interactions in ADPKD, relocating NHERF1 and NHERF2 from apical distributions back to intracellular vesicular compartments.

Pkd1RC/RC mice

A mouse model containing a missense mutation in $pkd1$ that recapitulates the slow onset of polycystic kidney disease typical of human ADPKD.

Proximity Ligation Assay (PLA)

An assay used to detect protein-protein interactions in situ when the target proteins are within $30-40\,nm$ of each other.

Ezrin

A protein linked to the cytoskeleton via the ERM domain that helps maintain membrane tension and junctional integrity; its localization is altered in PKD models.

PN cells

$Pkd1^{-/-}$ (knockout) proximal tubule cell lines that exhibit high cAMP levels and altered $Ca^{2+}$ signaling, used to model ADPKD.

PH cells

$Pkd1^{+/-}$ (heterozygous) proximal tubule cell lines used as controls in ADPKD research.

EENKVR

A six-amino acid sequence upstream of the C-terminus of CFTR necessary for the preferential localization of the channel at the apical membrane.

ERM domain

The ezrin/radixin/moesin domain which links NHERF proteins to the cellular cytoskeleton.

C-band

A specific band detected in Western blot experiments indicative of mature, fully glycosylated CFTR.

Scaffold "locational switch"

A pathological feature in ADPKD where CFTR–NHERF complexes move from intracellular vesicular compartments to being concentrated at the apical membrane.

PDZ domain

A binding motif in scaffold proteins like NHERF1 and NHERF2 that interacts with the C-terminal PDZ-binding motif of CFTR to anchor it in the plasma membrane.