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- Title
Independent Pathways Downstream of the Wnd/DLK MAPKKK Regulate Synaptic Structure, Axonal Transport, and Injury Signaling.
- Authors
Klinedinst, Susan; Wang, Xin; Xiong, Xin; Haenfler, Jill M.; Collins, Catherine A.
- Abstract
Mitogen-activated protein (MAP) kinase signaling cascades orchestrate diverse cellular activities with common molecular players. To achieve specific cellular outcomes in response to specific signals, scaffolding proteins play an important role. Here we investigate the role of the scaffolding protein JNK interacting protein-1 (JIPI) in neuronal signaling by a conserved axonal MAP kinase kinase kinase, known as Wallenda (Wnd) in Drosophila and dual leucine kinase (DLK) in vertebrates and Caenorhabditis elegans. Recent studies in multiple model organisms suggest that Wnd/DLK regulates both regenerative and degenerative responses to axonal injury. Here we report a new role for Wnd in regulating synaptic structure during development, which implies that Wnd is also active in uninjured neurons. This synaptic role of Wnd can be functionally separated from the role of Wnd in axonal regeneration and injury signaling by the requirement for the JIPI scaffold and the p38b MAP kinase. JIPI mediates the synaptic function of Wnd via p38, which is not required for injury signaling or new axonal growth after injury. Our results indicate that Wnd regulates multiple independent pathways in Drosophila motoneurons and that JIPI scaffolds a specific downstream cascade required for the organization of presynaptic microtubules during synaptic development.
- Subjects
NEURAL pathways; AXONAL transport; CELLULAR signal transduction; DEVELOPMENTAL neurobiology; SYNAPSES; MICROTUBULES
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 31, p12764
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.5160-12.2013