期刊
CURRENT BIOLOGY
卷 18, 期 3, 页码 221-226出版社
CELL PRESS
DOI: 10.1016/j.cub.2008.01.025
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资金
- Biotechnology and Biological Sciences Research Council Funding Source: Medline
- Medical Research Council [G0400620] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
- Medical Research Council [G0400620] Funding Source: researchfish
- MRC [G0400620] Funding Source: UKRI
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. JIP1 associates 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.
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