The Partial Rescue of the Axonal Guidance Defect of the Telencephalic Commissures of the JSAP1 Deficient Brain by the Transgenic Expression of JIP1

초록

The JNK interacting protein, JSAP1, has been previously identified in in vitro studies as a scaffold protein for MAPK signaling pathways and as a linker protein for the cargo transport along the axons. To investigate the physiological function of JSAP1 in vivo, we generated mice lacking JSAP1. The JSAP1 null mutation produced various deficits in the developing brain, including an axon guidance defect of the corpus callosum, in which phospho-JNK and phospho-FAK were distributed at abnormally reduced levels. The JSAP1 null mutation caused an impairment in the transport of the Ca+2 regulating protein, calretinin, but not the synaptic vesicle marker, SNAP-25, along the axons of the thalamocortical tract. The axon guidance defect of the corpus callosum in the jsap1-/- brain was also correlated with the misplacement of glial sling cells, which reverted to their normal position after the transgenic expression of JIP1 under the control of the PDGFb promoter. Furthermore, the transgenic JIP1 partially rescued the axon guidance defect of the corpus callosum and the anterior commissure of the jsap1-/- brain. These results suggest that the JSAP1 regulates various cellular processes in vivo through multiple mechanisms, and that the signaling network organized commonly by JIP1 and JSAP1 is required for the axon guidance in the developing brain.