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The JIP1 scaffold protein regulates axonal development in cortical neurons.

ABSTRACT: 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.

SUBMITTER: Dajas-Bailador F

PROVIDER: S-EPMC2258314 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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The JIP1 scaffold protein regulates axonal development in cortical neurons.

Dajas-Bailador Federico F Jones Emma V EV Whitmarsh Alan J AJ

Current biology : CB 20080201 3

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, ...[more]

PMID: 18261906

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The JIP1 scaffold protein regulates axonal development in cortical neurons.

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The JIP1 scaffold protein regulates axonal development in cortical neurons.

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