Related Experiment Video

Updated: Jun 12, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Cdk5-mediated phosphorylation of delta-catenin regulates its localization and GluR2-mediated synaptic activity

Charlene P Poore1, Jeyapriya R Sundaram, Tej K Pareek

  • 1Department of Biochemistry, Neurobiology Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|June 25, 2010
PubMed

Insights

Cyclin-dependent kinase 5 (Cdk5) phosphorylation of delta-catenin impacts synaptic function. Non-phosphorylated delta-catenin enhances dendritic spine formation and AMPA receptor activity, revealing a novel mechanism for synaptic plasticity.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Cyclin-dependent kinase 5 (Cdk5) is crucial for nervous system development and synaptic function.
  • Cdk5 activity influences neuronal migration and cortical lamination.
  • Delta-catenin, a synaptic adherens junction protein, anchors AMPA receptors at the postsynaptic membrane.

Purpose of the Study:

  • To investigate the role of Cdk5-mediated phosphorylation of delta-catenin in regulating synaptic activity.
  • To elucidate how Cdk5 phosphorylation affects delta-catenin's subcellular localization and dendritic morphogenesis.
  • To determine the impact of delta-catenin phosphorylation on AMPA receptor trafficking and synaptic transmission.

Main Methods:

  • Identification of Cdk5 phosphorylation sites in mouse delta-catenin (Ser300 and Ser357).
  • Mutation of phosphorylation sites to alanine to mimic non-phosphorylated delta-catenin.
  • Analysis of delta-catenin subcellular localization using microscopy.
  • Assessment of dendritic morphology and spine density.
  • Measurement of AMPA receptor subunit GluR2 localization.
  • Electrophysiological recordings to determine AMPA/NMDA ratios.

Main Results:

  • Cdk5 phosphorylation regulates delta-catenin's subcellular localization.
  • Loss of Cdk5 phosphorylation increases delta-catenin membrane localization.
  • Non-phosphorylated delta-catenin mutants exhibit increased dendritic protrusions and GluR2 membrane localization.
  • Disruption of Cdk5 phosphorylation enhances the AMPA/NMDA ratio, indicating increased excitatory synaptic transmission.

Conclusions:

  • Cdk5-mediated phosphorylation of delta-catenin is a key regulator of its synaptic localization and function.
  • Altered delta-catenin phosphorylation impacts dendritic morphogenesis and AMPA receptor trafficking.
  • This mechanism influences neuronal synaptic activity and plasticity by modulating the AMPA/NMDA ratio.

More Related Videos

Genetic Manipulation of Cerebellar Granule Neurons In Vitro and In Vivo to Study Neuronal Morphology and Migration09:07

Genetic Manipulation of Cerebellar Granule Neurons In Vitro and In Vivo to Study Neuronal Morphology and Migration

Published on: March 17, 2014

Isolation of CA1 Nuclear Enriched Fractions from Hippocampal Slices to Study Activity-dependent Nuclear Import of Synapto-nuclear Messenger Proteins10:03

Isolation of CA1 Nuclear Enriched Fractions from Hippocampal Slices to Study Activity-dependent Nuclear Import of Synapto-nuclear Messenger Proteins

Published on: August 10, 2014

Related Concept Videos

Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
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,...
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...