Two cytokine signaling molecules co-operate to promote axonal transport and growth.
The neuropoietic cytokines and their cytoplasmic signaling molecules contribute to axotomy-induced events in the nerve cell body that are beneficial to axonal regeneration. Previous studies have revealed a paradox in that, in vivo, suppressor of cytokine signaling (SOCS3) is induced in axotomized primary sensory neurons which are in a growth mode but, in vitro, SOCS3 strongly inhibits neurite growth from the same neurons. The present studies in cell lines with immuno-precipitation and western blotting, and Förstner resonance energy transfer showed that SOCS3 binds to the C terminus of C-Jun N-terminal kinase-interacting protein-1 (JIP1), increases its serine phosphorylation, and increases its binding to kinesin. Axonal transport was studied in vitro in adult rat primary sensory neurons by analyses of recovery of fluorescence after photobleaching and of the velocity and direction of movement of organelles. Over-expression of SOCS3 in addition to JIP1 had two consequences. First, recovery of fluorescence after photobleaching was more rapid and, second, JIP1-containing organelles moved more quickly and more frequently in retrograde direction. With respect to neurite outgrowth, SOCS3 alone was, as expected, strongly inhibitory but, in the presence of excess JIP1 augmented the stimulatory activity of the latter. The observations indicate that interactions between JIP1 and SOCS3 influence favorably axonal transport and growth in vitro.
Miao
T
T
Centre for Neuroscience, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, London E1 2AT, UK.
Wu
D
D
Wheeler
A
A
Wang
P
P
Zhang
Y
Y
Bo
X
X
Yeh
J S
JS
Subang
M C
MC
Richardson
P M
PM
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001370:Axonal Transport / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D006131:Growth Inhibitors / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D051379:Mice; D016501:Neurites / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D006131:Growth Inhibitors; C110528:Mapk8ip1 protein, rat; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D012694:Serine; D016547:Kinesins