PMID:21297631

Citation	Westerlund, N, Zdrojewska, J, Padzik, A, Komulainen, E, Björkblom, B, Rannikko, E, Tararuk, T, Garcia-Frigola, C, Sandholm, J, Nguyen, L, Kallunki, T, Courtney, MJ and Coffey, ET (2011) Phosphorylation of SCG10/stathmin-2 determines multipolar stage exit and neuronal migration rate. Nat. Neurosci. 14:305-13
Abstract	Cell migration is the consequence of the sum of positive and negative regulatory mechanisms. Although appropriate migration of neurons is a principal feature of brain development, the negative regulatory mechanisms remain obscure. We found that JNK1 was highly active in developing cortex and that selective inhibition of JNK in the cytoplasm markedly increased both the frequency of exit from the multipolar stage and radial migration rate and ultimately led to an ill-defined cellular organization. Moreover, regulation of multipolar-stage exit and radial migration in Jnk1(-/-) (also known as Mapk8) mice, resulted from consequential changes in phosphorylation of the microtubule regulator SCG10 (also called stathmin-2). Expression of an SCG10 mutant that mimics the JNK1-phosphorylated form restored normal migration in the brains of Jnk1(-/-) mouse embryos. These findings indicate that the phosphorylation of SCG10 by JNK1 is a fundamental mechanism that governs the transition from the multipolar stage and the rate of neuronal cell movement during cortical development.
Links	PubMed Online version:10.1038/nn.2755
Keywords	Animals; Cell Movement/physiology; Cerebral Cortex/cytology; Cerebral Cortex/embryology; Cerebral Cortex/growth & development; Cerebral Cortex/metabolism; Gene Expression Regulation; Intracellular Signaling Peptides and Proteins/genetics; Intracellular Signaling Peptides and Proteins/metabolism; Mice; Mice, Knockout; Mitogen-Activated Protein Kinase 8/antagonists & inhibitors; Mitogen-Activated Protein Kinase 8/genetics; Mitogen-Activated Protein Kinase 8/metabolism; Neurons/physiology; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Tubulin/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:MK08		GO:0001764: neuron migration	ECO:0000315:		P		Figure 2E, JNK1 deficient neurons migrate faster than wild type neurons, as 3 times as many JNK deficient cells had migrated. Figure 7E supports this, showing that JNK deficient cells migrate at a faster speed in a time lapse study. JNK1 is involved in migration of neurons.	complete CACAO 4638
MOUSE:MK08	involved_in	GO:0001764: neuron migration	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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