The axon guidance defect of the telencephalic commissures of the JSAP1-deficient brain was partially rescued by the transgenic expression of JIP1.
The JNK interacting protein, JSAP1, has been identified as a scaffold protein for mitogen-activated protein kinase (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 developmental deficits in the brain, including an axon guidance defect of the corpus callosum, in which phospho-FAK and phospho-JNK were distributed at reduced levels. The axon guidance defect of the corpus callosum in the jsap1-/- brain was correlated with the misplacement of glial sling cells, which reverted to their normal position after the transgenic expression of JNK interacting protein 1(JIP1). The transgenic JIP1 partially rescued the axon guidance defect of the corpus callosum and the anterior commissure of the jsap1-/- brain. The JSAP1 null mutation impaired the normal distribution of the Ca+2 regulating protein, calretinin, but not the synaptic vesicle marker, SNAP-25, along the axons of the thalamocortical tract. These results suggest that JSAP1 is required for the axon guidance of the telencephalic commissures and the distribution of cellular protein(s) along axons in vivo, and that the signaling network organized commonly by JIP1 and JSAP1 regulates the axon guidance in the developing brain.
Ha
Hye-Yeong
HY
Department of Neuroscience, Neuroscience Research Center and Medical Research Institute, Ewha Womans University School of Medicine, Seoul 110-783, Korea.
Cho
Ik-Hyun
IH
Lee
Kang-Woo
KW
Lee
Ko-Woon
KW
Song
Ji-Young
JY
Kim
Kyoung-Shim
KS
Yu
Young-Mi
YM
Lee
Ja-Kyeong
JK
Song
Jin-Sook
JS
Yang
Sung-Don
SD
Shin
Hee-Sup
HS
Han
Pyung-Lim
PL
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D002540:Cerebral Cortex / Q000196:embryology; D003337:Corpus Callosum / Q000166:cytology / Q000196:embryology*; D006624:Hippocampus / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009900:Optic Nerve / Q000196:embryology; D013788:Thalamus / Q000196:embryology
D048868:Adaptor Proteins, Signal Transducing; C490665:Mapk8ip protein, mouse; C403619:Mapk8ip3 protein, mouse; D009419:Nerve Tissue Proteins