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PMID:16618812

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Citation

Tararuk, T, Ostman, N, Li, W, Björkblom, B, Padzik, A, Zdrojewska, J, Hongisto, V, Herdegen, T, Konopka, W, Courtney, MJ and Coffey, ET (2006) JNK1 phosphorylation of SCG10 determines microtubule dynamics and axodendritic length. J. Cell Biol. 173:265-77

Abstract

c-Jun NH(2)-terminal kinases (JNKs) are essential during brain development, when they regulate morphogenic changes involving cell movement and migration. In the adult, JNK determines neuronal cytoarchitecture. To help uncover the molecular effectors for JNKs in these events, we affinity purified JNK-interacting proteins from brain. This revealed that the stathmin family microtubule-destabilizing proteins SCG10, SCLIP, RB3, and RB3' interact tightly with JNK. Furthermore, SCG10 is also phosphorylated by JNK in vivo on sites that regulate its microtubule depolymerizing activity, serines 62 and 73. SCG10-S73 phosphorylation is significantly decreased in JNK1-/- cortex, indicating that JNK1 phosphorylates SCG10 in developing forebrain. JNK phosphorylation of SCG10 determines axodendritic length in cerebrocortical cultures, and JNK site-phosphorylated SCG10 colocalizes with active JNK in embryonic brain regions undergoing neurite elongation and migration. We demonstrate that inhibition of cytoplasmic JNK and expression of SCG10-62A/73A both inhibited fluorescent tubulin recovery after photobleaching. These data suggest that JNK1 is responsible for regulation of SCG10 depolymerizing activity and neurite elongation during brain development.

Links

PubMed PMC2063817 Online version:10.1083/jcb.200511055

Keywords

Animals; Axons/physiology; Brain/growth & development; Carrier Proteins; Cell Line; Cells, Cultured; Dendrites/physiology; Embryo, Mammalian/cytology; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Mice; Microtubules/metabolism; Mitogen-Activated Protein Kinase 8/analysis; Mitogen-Activated Protein Kinase 8/antagonists & inhibitors; Mitogen-Activated Protein Kinase 8/metabolism; Nerve Growth Factors/metabolism; Phosphorylation; Rats; Recombinant Proteins/genetics; Recombinant Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:STMN2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:621506

F

Seeded From UniProt

complete

RAT:STMN2

located_in

GO:0030426: growth cone

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:STMN2

located_in

GO:0005794: Golgi apparatus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:STMN2

located_in

GO:0031982: vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:MK08

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:68947

F

Seeded From UniProt

complete

RAT:MK08

located_in

GO:0031982: vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:MK08

involved_in

GO:0031116: positive regulation of microtubule polymerization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:MK08

involved_in

GO:0031175: neuron projection development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:MK08

part_of

GO:0031982: vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

See also

References

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