title: Spatial phosphoprotein profiling reveals a compartmentalized extracellular signal-regulated kinase switch governing neurite growth and retraction.
abstract: 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.
authors: Department of Pathology and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
authors: Yingchun
authors: Y
authors: Wang
authors: Feng
authors: F
authors: Yang
authors: Yi
authors: Y
authors: Fu
authors: Xiahe
authors: X
authors: Huang
authors: Wei
authors: W
authors: Wang
authors: Xinning
authors: X
authors: Jiang
authors: Marina A
authors: MA
authors: Gritsenko
authors: Rui
authors: R
authors: Zhao
authors: Matthew E
authors: ME
authors: Monore
authors: Olivier C
authors: OC
authors: Pertz
authors: Samuel O
authors: SO
authors: Purvine
authors: Daniel J
authors: DJ
authors: Orton
authors: Jon M
authors: JM
authors: Jacobs
authors: David G
authors: DG
authors: Camp
authors: Richard D
authors: RD
authors: Smith
authors: Richard L
authors: RL
authors: Klemke
mesh_terms: D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D048049:Extracellular Signal-Regulated MAP Kinases