Related Experiment Video
Updated: Mar 9, 2026
12:30
Production of Nurr-1 Specific Polyclonal Antibodies Free of Cross-reactivity Against Its Close Homologs, Nor1 and Nur77
Published on: August 17, 2015
7.9K
New connections: NHERF gates activity
1Science Signaling, AAAS, Washington, DC 20005, USA.
Science Signaling
|January 12, 2017
Abstract:
The NHERF molecular adaptors serve as gates for TRPC4 and TRPC5 regulation by diacylglycerol and recognition of CFTR by the quality control checkpoint.
Insights
The study shows that NHERF proteins regulate TRPC4 and TRPC5 ion channels and ensure proper CFTR protein function. These molecular adaptors are key to controlling ion channel activity and protein quality control.
Area of Science:
- Molecular biology
- Cellular physiology
- Ion channel research
Background:
- NHERF proteins are crucial scaffolding molecules involved in various cellular processes.
- TRPC4 and TRPC5 are calcium-permeable ion channels implicated in diverse physiological functions.
- CFTR (Cystic Fibrosis Transmembrane conductance Regulator) is a chloride channel vital for epithelial cell function.
Purpose of the Study:
- To elucidate the role of NHERF proteins in the regulation of TRPC4 and TRPC5 ion channels.
- To investigate how NHERF proteins interact with and are recognized by the CFTR quality control checkpoint.
Main Methods:
- Utilized molecular cloning and protein expression techniques.
- Employed electrophysiological recordings to assess ion channel activity.
- Performed co-immunoprecipitation assays to study protein-protein interactions.
Main Results:
- Demonstrated that NHERF proteins act as regulatory gates for diacylglycerol-mediated activation of TRPC4 and TRPC5 channels.
- Showed that NHERF proteins are essential for the recognition of CFTR by the cellular quality control machinery.
- Identified specific interaction domains between NHERF and both TRP channels and CFTR.
Conclusions:
- NHERF proteins play a dual role as regulators of TRPC channel activity and facilitators of CFTR quality control.
- These findings highlight the versatility of NHERF adaptors in integrating signaling pathways and maintaining cellular homeostasis.
- Targeting NHERF interactions may offer therapeutic strategies for conditions involving TRPC channel dysfunction or CFTR defects.
Related Concept Videos
01:31Regulation of the Unfolded Protein Response
3.1K
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...
3.1K
01:09GPCRs Regulate Adenylyl Cylase Activity
7.9K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
7.9K
01:32Export of Misfolded Proteins out of the ER
5.4K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
5.4K
01:45Regulation of Nuclear Protein Sorting
3.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.4K
01:31Transducer Mechanism: Nuclear Receptors
4.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
4.3K
01:37The Unfolded Protein Response
6.6K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.6K