Related Experiment Video

Updated: May 18, 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 CRMP-2 enhances its interaction with CaV2.2

Joel M Brittain1, Yuying Wang, Omotore Eruvwetere

  • 1Program in Medical Neuroscience, Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, United States.

FEBS Letters
|October 2, 2012
PubMed

Insights

Cyclin-dependent kinase 5 (Cdk5) phosphorylation of collapsin response mediator protein-2 (CRMP-2) is crucial for its regulation of N-type voltage-gated calcium channels (CaV2.2). This phosphorylation enhances CRMP-2

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Signaling

Background:

  • Collapsin response mediator protein-2 (CRMP-2) is known to regulate N-type voltage-gated calcium channels (CaV2.2).
  • The specific role of Cdk5-mediated phosphorylation of CRMP-2 in this regulation remains unclear.

Purpose of the Study:

  • To investigate how Cdk5-mediated phosphorylation of CRMP-2 influences its interaction and regulatory function with CaV2.2 channels.
  • To elucidate the molecular mechanisms underlying CRMP-2's regulation of CaV2.2.

Main Methods:

  • Utilized a phospho-null CRMP-2-S522A mutant and inactive Cdk5 to assess the necessity of phosphorylation.
  • Employed knockdown of endogenous CRMP2 combined with overexpression of CRMP2 mutants (S522A and T555A) to evaluate functional effects.
  • Assessed the association between Cdk5-phosphorylated CRMP-2 and CaV2.2.

Main Results:

  • CRMP-2-mediated enhancement of CaV2.2 currents was abolished by the CRMP-2-S522A mutant and inactive Cdk5.
  • Knockdown of CRMP2 followed by overexpression of the phospho-null S522A mutant mimicked the reduction in Ca(2+) influx.
  • A CRMP2-T555A mutant (affecting Rho kinase site) did not affect Ca(2+) influx, indicating specificity.
  • Cdk5-phosphorylated CRMP-2 exhibited increased binding affinity to CaV2.2.

Conclusions:

  • Cdk5-mediated phosphorylation of CRMP-2 at serine 522 is essential for its positive regulatory effect on CaV2.2 channel activity.
  • This phosphorylation event enhances the association between CRMP-2 and CaV2.2, thereby modulating calcium influx.
  • Identifies a critical role for the Cdk5/CRMP-2 pathway in the regulation of CaV2.2 channels.

More Related Videos

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion09:23

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion

Published on: April 2, 2020

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Related Concept Videos

Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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...
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...
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.
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.