Related Experiment Video

Updated: Jun 28, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

A single mutation at lysine 241 alters expression and trafficking of the D2 dopamine receptor

Ok-Jin Kim1

  • 1Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, Kansas 66045-7582, USA. stevenleonardparker@msn.com

Journal of Receptor and Signal Transduction Research
|October 24, 2008
PubMed

Insights

The D2 dopamine receptor (DAR) is ubiquitinated, affecting its signaling and degradation. Loss of lysine-241 on D2 DAR impacts ubiquitination and leads to proteasomal degradation.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Neuroscience

Background:

  • G protein-coupled receptors (GPCRs) ubiquitination regulates signal transduction, including internalization and sorting.
  • Dopamine receptors (DARs) are key GPCRs involved in various neurological processes.

Purpose of the Study:

  • To investigate the role of ubiquitination in D2 dopamine receptor (DAR) regulation.
  • To identify specific sites of ubiquitination on D2 DAR and their functional consequences.

Main Methods:

  • Co-immunoprecipitation and immunoblot analysis were used to detect ubiquitination.
  • Site-directed mutagenesis was employed to create a K241A D2 DAR mutant.
  • Human embryonic kidney cells (HEK293) were utilized for receptor expression.

Main Results:

  • Membrane-associated D2 DAR was found to be mono-ubiquitinated in the absence of an agonist.
  • A K241A D2 DAR mutant showed reduced membrane association and altered ubiquitination patterns.
  • The ubiquitinated K241A D2 DAR mutant was degraded via the ubiquitin-proteasome pathway.

Conclusions:

  • Lysine-241 is crucial for D2 DAR ubiquitination.
  • Loss of lysine-241 leads to increased susceptibility of D2 DAR to proteasomal degradation.
  • Ubiquitination plays a significant role in regulating D2 DAR stability and signaling.

More Related Videos

Assaying the Kinase Activity of LRRK2 in vitro06:09

Assaying the Kinase Activity of LRRK2 in vitro

Published on: January 18, 2012

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate11:31

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate

Published on: September 18, 2013

Related Concept Videos

Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
Drugs Affecting Neurotransmitter Synthesis01:29

Drugs Affecting Neurotransmitter Synthesis

Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase, which converts...
Mutations01:39

Mutations

Overview
Parkinson Disease ll: Pathophysiology01:24

Parkinson Disease ll: Pathophysiology

Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
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...