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

Brain development and spinal cord regeneration require neurite sprouting and growth cone navigation in response to extension and collapsing factors present in the extracellular environment. These external guidance cues control neurite growth cone extension and retraction processes through intracellu...

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Bibliographic Details
Published in:The Journal of biological chemistry 2011-05, Vol.286 (20), p.18190-18201
Main Authors: Wang, Yingchun, Yang, Feng, Fu, Yi, Huang, Xiahe, Wang, Wei, Jiang, Xinning, Gritsenko, Marina A., Zhao, Rui, Monore, Matthew E., Pertz, Olivier C., Purvine, Samuel O., Orton, Daniel J., Jacobs, Jon M., Camp, David G., Smith, Richard D., Klemke, Richard L.
Format: Article
Language:English
Subjects:
ABL Tyrosine Kinase
Activated Protein-Kinase
ADHESION
Adult DRG Neurons
Axon guidance
BASIC BIOLOGICAL SCIENCES
BRAIN
Cell Biology
Cell Line
Cell-Migration
Cone Guidance
CONES
Cytoskeletal Dynamics
Environmental Molecular Sciences Laboratory
ERK
ERK Activation
Extracellular Signal-Regulated MAP Kinases - genetics
Extracellular Signal-Regulated MAP Kinases - metabolism
FUNCTIONALS
GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
Humans
Kinases
Lysophosphatidic Acid
MAP Kinase Signaling System - physiology
Map-Kinase
MASS SPECTROSCOPY
NAVIGATION
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Neurites - metabolism
Neuron
PHOSPHOPROTEINS
Phosphoproteins - genetics
Phosphoproteins - metabolism
Phosphorylase
PHOSPHORYLATION
PHOSPHOTRANSFERASES
Phosphotyrosine
PROTEINS
Proteomics
PURIFICATION
REGENERATION
SPINAL CORD
SPROUTING
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Summary:Brain development and spinal cord regeneration require neurite sprouting and growth cone navigation in response to extension and collapsing factors present in the extracellular environment. These external guidance cues control neurite growth cone extension and retraction processes through intracellular protein phosphorylation of numerous cytoskeletal, adhesion, and polarity complex signaling proteins. However, the complex kinase/substrate signaling networks that mediate neuritogenesis have not been investigated. Here, we compare the neurite phosphoproteome under growth and retraction conditions using neurite purification methodology combined with mass spectrometry. More than 4000 non-redundant phosphorylation sites from 1883 proteins have been annotated and mapped to signaling pathways that control kinase/phosphatase networks, cytoskeleton remodeling, and axon/dendrite specification. Comprehensive informatics and functional studies revealed a compartmentalized ERK activation/deactivation cytoskeletal switch that governs neurite growth and retraction, respectively. Our findings provide the first system-wide analysis of the phosphoprotein signaling networks that enable neurite growth and retraction and reveal an important molecular switch that governs neuritogenesis.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M111.236133