Related Experiment Video

Updated: May 31, 2026

Direct Imaging of ER Calcium with Targeted-Esterase Induced Dye Loading (TED)
09:32

Direct Imaging of ER Calcium with Targeted-Esterase Induced Dye Loading (TED)

Published on: May 7, 2013

Polycystin-1, 2, and STIM1 interact with IP(3)R to modulate ER Ca release through the PI3K/Akt pathway

Netty G Santoso1, Liudmila Cebotaru, William B Guggino

  • 1Department of Physiology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
|June 22, 2011
PubMed

Insights

Polycystins (PC1 and PC2) regulate calcium (Ca2+) signaling in autosomal dominant polycystic kidney disease (ADPKD). PC1 expression reduces Ca2+ release by altering interactions between PC2, IP3R, and STIM1 via the PI3K/Akt pathway.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • Autosomal dominant polycystic kidney disease (ADPKD) is linked to calcium (Ca2+) signaling dysregulation.
  • Polycystins (PC1 and PC2) are implicated in ADPKD pathogenesis through aberrant Ca2+ homeostasis.
  • Understanding polycystin function in Ca2+ signaling is crucial for ADPKD research.

Purpose of the Study:

  • To investigate the role of polycystins (PC1 and PC2) in modulating intracellular Ca2+ signaling.
  • To elucidate the molecular interactions governing Ca2+ release in the context of PC1 expression.
  • To explore the involvement of the PI3K/Akt signaling pathway in polycystin-mediated Ca2+ regulation.

Main Methods:

  • Utilized Madin-Darby canine kidney (MDCK) cells for experimental models.
  • Assessed intracellular Ca2+ release in response to ATP.
  • Investigated protein-protein interactions using co-immunoprecipitation (PC2, IP3R, STIM1).
  • Manipulated the PI3K/Akt signaling pathway using inhibitors and activators (HGF).

Main Results:

  • PC1 expression in MDCK cells inhibited ATP-induced intracellular Ca2+ release.
  • PC1 expression reduced the interaction between PC2 and IP3R.
  • PC1 expression enhanced the interaction between STIM1 and IP3R, further inhibiting Ca2+ release.
  • The PI3K/Akt pathway mediates PC1's effects on Ca2+ signaling and protein interactions.
  • Modulating PI3K/Akt reversed or mimicked PC1's effects on Ca2+ release and protein complex formation.

Conclusions:

  • Polycystins, particularly PC1, play a significant role in regulating intracellular Ca2+ release.
  • PC1 modulates Ca2+ signaling by altering the PC2-IP3R-STIM1 complex formation through the PI3K/Akt pathway.
  • These findings offer a potential mechanism for polycystin-mediated Ca2+ signaling dysregulation in ADPKD.

More Related Videos

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins11:25

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins

Published on: October 4, 2017

Related Concept Videos

IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...