JNK1 phosphorylation of SCG10 determines microtubule dynamics and axodendritic length.
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.
Tararuk
Tatsiana
T
Turku Centre for Biotechnology, Turku, FIN-20521, Finland.
Ostman
Nina
N
Li
Wenrui
W
Björkblom
Benny
B
Padzik
Artur
A
Zdrojewska
Justyna
J
Hongisto
Vesa
V
Herdegen
Thomas
T
Konopka
Witold
W
Courtney
Michael J
MJ
Coffey
Eleanor T
ET
D000818:Animals; D001369:Axons / Q000502:physiology*; D001921:Brain / Q000254:growth & development; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D002460:Cell Line; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D008868:Microtubule Proteins; D008870:Microtubules / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D050777:Stathmin
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008868:Microtubule Proteins; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D050777:Stathmin; C512849:Stmn2 protein, mouse; C512848:Stmn2 protein, rat; D048055:Mitogen-Activated Protein Kinase 8