CRMP5 (collapsin response mediator protein 5) regulates dendritic development and synaptic plasticity in the

Naoya Yamashita1, Bedrich Mosinger, Arpita Roy

  • 1Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.

Insights

Collapsin response mediator protein 5 (CRMP5) deficiency impairs cerebellar Purkinje cell development and synaptic plasticity. CRMP5 is crucial for brain-derived neurotrophic factor (BDNF) signaling, impacting neuronal structure and function.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Developmental Biology

Background:

  • Collapsin response mediator protein 5 (CRMP5) is abundant in the developing brain.
  • CRMP family proteins play roles in neuronal development and axon guidance.

Purpose of the Study:

  • To investigate the in vivo function of CRMP5 in cerebellar development and synaptic plasticity.
  • To elucidate the role of CRMP5 in brain-derived neurotrophic factor (BDNF) signaling.

Main Methods:

  • Generation of crmp5-deficient (crmp5(-/-)) mice.
  • Immunofluorescence studies of cerebellar Purkinje cells.
  • Electrophysiological recordings in cerebellar slices.
  • Neuronal culture and stimulation with BDNF.

Main Results:

  • crmp5(-/-) mice exhibited aberrant Purkinje cell dendrite morphology and reduced soma size.
  • Deficient long-term depression of excitatory synaptic transmission in crmp5(-/-) cerebellar slices.
  • BDNF-induced dendritic branching was attenuated in cultured crmp5(-/-) neurons.
  • CRMP5 was tyrosine phosphorylated upon coexpression with TrkB, the BDNF receptor.

Conclusions:

  • CRMP5 is essential for the proper development, maintenance, and synaptic plasticity of cerebellar Purkinje cells.
  • CRMP5 plays a significant role in BDNF signaling pathways, influencing neuronal structure and function.

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

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...
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,...
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...
The Unfolded Protein Response01:37

The Unfolded Protein Response

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...
Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...