2007 Fiscal Year Final Research Report Summary
Analysis of LRK-1 kinase which regulates polarized sorting in neurons
| Project/Area Number |
18570174
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Nagoya University |
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Principal Investigator |
HISAMOTO Naoki Nagoya University, Biological Science, Associate professor (80283456)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Polarized transport / kinase / neuron / C.elegans |
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| Research Abstract |
Neurons are polarized cells that contain distinct sets of proteins in their axons and dendrites. Synaptic vesicles(SV)and many SV proteins are exclusively localized in the presynaptic regions but not in dendrites. Despite their fundamental importance, the mechanisms underlying the polarized localization of SV proteins remain unclear. The transparent nematode Caenorhabditis elegans can be used to examine sorting and transport of SV proteins in vivo. Here, we identify a novel protein kinase LRK-1, a C. elegans homolog of the familial Parkinsonism gene PARK8/LRRK2 that is required for polarized localization of SV proteins. In Irk-1 deletion mutants, SV proteins are localized to both presynaptic and dendritic endings in neurons. This aberrant localization of SV proteins in the dendrites is dependent on the AP-1 ml clathrin adaptor UNC-101, which is involved in polarized dendritic transport, but not on UNC-I 04 kinesin, which is required for the transport of SV to presynaptic regions. The LRK-1 proteins are localized in the Golgi apparatus. These results suggest that the LRK-1 protein kinase determines polarized sorting of SV proteins to the axons by excluding SV proteins from the dendrite-specific transport machinery in the Golgi.
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