The JIP1 scaffold protein regulates axonal development in cortical neurons

Curr Biol. 2008 Feb 12;18(3):221-6. doi: 10.1016/j.cub.2008.01.025.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Axons / metabolism*
  • Cerebral Cortex / cytology*
  • Gene Expression Regulation
  • Mice
  • Neurons / cytology*
  • Neurons / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-abl / metabolism


  • Adaptor Proteins, Signal Transducing
  • Mapk8ip protein, mouse
  • Proto-Oncogene Proteins c-abl