Spatial Phosphoprotein Profiling Reveals a Compartmentalized Extracellular Signal-regulated Kinase Switch Governing Neurite Growth and Retraction

JBC, 2011 · DOI: 10.1074/jbc.M111.236133 · Published: May 20, 2011

Simple Explanation

Brain development and spinal cord regeneration depend on neurite sprouting and growth cone navigation, guided by extracellular extension and collapsing factors. These cues control neurite growth and retraction via intracellular protein phosphorylation, affecting cytoskeletal, adhesion, and polarity complex signaling proteins. This study compares the neurite phosphoproteome during growth and retraction, revealing a compartmentalized ERK switch governing these processes.

Study Duration

Not specified

Participants

NIE-115 cells

Evidence Level

Not specified

Key Findings

1
Identified over 4000 non-redundant phosphorylation sites from 1883 proteins, mapping to signaling pathways controlling kinase/phosphatase networks, cytoskeleton remodeling, and axon/dendrite specification.
2
Comprehensive analysis revealed a compartmentalized ERK activation/deactivation cytoskeletal switch that governs neurite growth and retraction, respectively.
3
Integrins spatially regulate MEK phosphorylation/activation during neurite growth and retraction.

Research Summary

This study profiles phosphoprotein signaling networks in neurites during growth and retraction to identify key regulatory mechanisms. Microporous filter method was used to purify neurites, followed by mass spectrometry to identify thousands of protein phosphorylation signatures. The findings reveal a critical integrin/MEK/ERK signaling pathway operating as a switch controlling neurite extension and retraction dynamics.

Practical Implications

Neurite growth and retraction

Integrin/MEK/ERK signaling pathway is a switch that controls neurite extension and retraction.

Brain Development and Spinal Cord Regeneration

Understanding neuronal growth cone spatial interpretation of extracellular cues is critical for proper brain development and spinal cord regeneration.

Targeted Therapies

The study identifies potential targets for therapeutic interventions aimed at promoting nerve regeneration or preventing neurodegenerative processes.

Study Limitations

1
The study uses an in vitro model (NIE-115 cells), which may not fully represent the complexity of in vivo neuronal behavior.
2
The phosphoproteomic analysis provides a snapshot of phosphorylation events but doesn't fully capture the dynamics of signaling pathways over time.
3
Further research is needed to validate the identified kinase-substrate relationships and their functional roles in neuritogenesis.

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