The JIP1 scaffold protein regulates axonal development in cortical neurons.
The development of neuronal polarity is essential for the determination of neuron connectivity and for correct brain function. The c-Jun N-terminal kinase (JNK)-interacting protein-1 (JIP1) is highly expressed in neurons and has previously been characterized as a regulator of JNK signaling.JIP1 has been shown to localize to neurites in various neuronal models, but the functional significance of this localization is not fully understood [1-4]. JIP1 is also a cargo of the motor protein kinesin-1, which is important for axonal transport [2, 4]. Here we demonstrate that before primary cortical neurons become polarized, JIP1 specifically localizes to a single neurite and that after axonal specification,it accumulates in the emerging axon. JIP1 is necessary for normal axonal development and promotes axonal growth dependent upon its binding to kinesin-1 and via a newly described interaction with the c-Abl tyrosine kinase. JIP1associates with and is phosphorylated by c-Abl, and the mutation of the c-Abl phosphorylation site on JIP1 abrogates its ability to promote axonal growth. JIP1 is therefore an important regulator of axonal development and is a key target of c-Abl-dependent pathways that control axonal growth.
Dajas-Bailador
Federico
F
Faculty of Life Sciences, Michael Smith Building, University of Manchester, Oxford Road, Manchester, M13 9PT, United Kingdom.
Jones
Emma V
EV
Whitmarsh
Alan J
AJ
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology*; D005786:Gene Expression Regulation; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C490665:Mapk8ip protein, mouse; D016315:Proto-Oncogene Proteins c-abl