Related Experiment Video

Updated: Jun 22, 2026

Isolation and Quantification of Axonal mRNAs Using Porous Membrane Inserts and RTddPCR
07:06

Isolation and Quantification of Axonal mRNAs Using Porous Membrane Inserts and RTddPCR

Published on: February 6, 2026

P90 Ribosomal s6 kinase 2 negatively regulates axon growth in motoneurons

Matthias Fischer1, Patricia Marques Pereira, Bettina Holtmann

  • 1Institute for Clinical Neurobiology, University of Würzburg, 97080 Würzburg, Germany. fischer_m2@klinik.uni-wuerzburg.de

Molecular and Cellular Neurosciences
|June 27, 2009
PubMed

Insights

Ribosomal s6 kinase 2 (Rsk2) deficiency causes longer neurites in mouse neurons by inhibiting the MAPK pathway. This dysregulated neurite growth, not neurodegeneration, may explain Coffin-Lowry syndrome

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Mutations in Ribosomal s6 kinase 2 (Rsk2) are linked to Coffin-Lowry syndrome (CLS), causing severe neuronal dysfunction.
  • The precise mechanisms by which Rsk2 regulates neuronal development, maintenance, and activity remain unclear.

Purpose of the Study:

  • To investigate the role of Rsk2 in mouse spinal motoneurons.
  • To elucidate the molecular pathways affected by Rsk2 deficiency in neurons.

Main Methods:

  • Isolated Rsk2-deficient mouse spinal motoneurons were analyzed for survival and neurite outgrowth.
  • The effect of Rsk2 overexpression on axon growth was examined.
  • Erk 1/2 phosphorylation levels and the impact of MAPK/Erk kinase (Mek) inhibition were assessed.

Main Results:

  • Rsk2-deficient motoneurons exhibited normal survival but significantly increased neurite elongation.
  • Overexpression of active Rsk2 resulted in reduced axon growth.
  • Increased axon growth in Rsk2-deficient neurons correlated with elevated Erk 1/2 phosphorylation, and this phenotype was rescued by Mek inhibition.

Conclusions:

  • Rsk2 acts as a negative regulator of axon elongation through the MAPK pathway.
  • Dysregulated neurite growth, rather than primary neurodegeneration, is likely responsible for the nervous system defects observed in CLS patients and animal models with Rsk2 deficiency.

More Related Videos

Standardization of a Novel Semi-Automatic Software for Neurite Outgrowth Measurement05:28

Standardization of a Novel Semi-Automatic Software for Neurite Outgrowth Measurement

Published on: August 9, 2024

Detection of Axonally Localized mRNAs in Brain Sections Using High-Resolution In Situ Hybridization11:24

Detection of Axonally Localized mRNAs in Brain Sections Using High-Resolution In Situ Hybridization

Published on: June 17, 2015

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...