Research Abstract:
My laboratory's research is focused on understanding the molecular mechanisms orchestrating the response of neurons to axonal injury in the mouse model system. Most parts of the adult CNS cannot regenerate axons following damage, resulting in the devastating conditions of paralysis following spinal-cord injury. Despite the identification of numerous molecules that influence regeneration, the mechanisms underlying axonal growth following injury are still poorly understood. Currently, two main areas are under investigation. First, we are focusing on understanding how information from the site of injury in the axon is communicated to the cell body. We reported previously that the kinesin binding protein Sunday Driver, in collaboration with the stress-activated protein kinase JNK and the molecular motor system establishes a vesicular axonal damage signaling system. To better understand Sunday Driver function in injury signaling, we have developed a biochemical approach to purify Sunday Driver vesicles. Mass spectrometry analyses allowed us to identify proteins residing on these vesicles. We will further investigate the role of these proteins in injury signaling by a combination of biochemistry, cell biology, molecular biology and in vivo imaging. Second, we are dissecting the role of anterograde axonal transport and membrane trafficking in axonal growth during development and regeneration. We have identified another population of small axonal vesicles with which Sunday Driver is associated. Theses vesicles are found at the synaptic terminal but are morphologically and functionally distinct from synaptic vesicles. In vivo imaging and genetic approaches will be used in addition to cell biology and biochemistry to study the role of candidate proteins in axonal elongation. The long-term goal of our research is to provide a better understanding of the molecular determinants leading to successful axonal regeneration, which will be a key step towards improving our ability to restore nerve function following damage.
Selected Publications:
Abe N and Cavalli V. Nerve injury signaling, Curr Opin Neurobiol. 2008 18:1-8 PMID: 18655834.
Cavalli V. Transport dependent damage signaling. In Larry R. Squire, Editor-in-Chief, Encyclopedia of Neuroscience, Academic Press, Oxford 2008.
Cavalli V, Kujala P, Klumperman J and Goldstein LS. Sunday driver links axonal transport to damage signaling. J Cell Biol 2005 168: 775-787.
Cavalli V, Corti M, and Gruenberg J. Endocytosis and signaling cascades: a close encounter. FEBS Lett 2001 498: 190-196.
Cavalli V, Vilbois F, Corti M, Marcote MJ, Tamura K, Karin M, Arkinstall S, and Gruenberg J. The stress induced MAP Kinase p38 regulates endocyic trafficking via the GDI:Rab5 complex. Mol Cell 2001 7:421-432.
Last Updated: 11/13/2008 |