Casein kinase ii (protein kinase ck2) regulates serotonin 5-ht(3) receptor channel function in ng108-15 cells

S Jones1, J L Yakel

  • 1Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, P.O. Box 12233, 27709, Research Triangle Park, NC, USA.

Neuroscience
|June 18, 2003
PubMed

Insights

Protein kinase CK2 enhances serotonin 5-HT(3) receptor function. This enzyme increases the amplitude and slows the desensitization of 5-HT(3) receptor channels, suggesting a key regulatory role in the nervous system.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Physiology

Background:

  • The serotonin 5-HT(3) receptor (5-HT(3)R) is a ligand-gated ion channel crucial for neurotransmission.
  • Protein kinase CK2 (CK2) is a ubiquitous serine/threonine kinase implicated in various cellular processes.

Purpose of the Study:

  • To investigate the modulatory effect of protein kinase CK2 on the function of the serotonin 5-HT(3) receptor channel.
  • To determine if CK2 influences the amplitude and desensitization kinetics of 5-HT(3)R-mediated currents.

Main Methods:

  • Whole-cell patch-clamp recording techniques were employed in the NG108-15 cell line.
  • Internal dialysis of cells with active or heat-inactivated protein kinase CK2 was performed via patch pipettes.
  • Rapid application of serotonin (5-HT) was used to elicit and measure 5-HT(3)R-mediated currents.

Main Results:

  • Internal dialysis with active CK2 significantly increased the amplitude of 5-HT(3)R-mediated inward currents.
  • Active CK2 significantly decreased the rate of desensitization of these currents.
  • Heat-inactivated CK2 had no significant effect on current amplitude or desensitization kinetics, indicating the enzymatic activity of CK2 is required.

Conclusions:

  • Protein kinase CK2 significantly enhances the function of the serotonin 5-HT(3) receptor channel.
  • CK2 may act as a critical regulator of 5-HT(3)R activity in the nervous system.
  • CK2 could facilitate 5-HT-induced cellular excitation by modulating 5-HT(3)R function.

Related Concept Videos

G-protein Coupled Receptors01:21

G-protein Coupled Receptors

G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
What are Second Messengers?01:12

What are Second Messengers?

Because many receptor binding ligands are hydrophilic, they do not cross the cell membrane and thus their message must be relayed to a second messenger on the inside. There are several second messenger pathways, each with their own way of relaying information. G-protein coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol path is active when the receptor induces phospholipase C to hydrolyze the phospholipid,...
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

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 cells.
Two...
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,...