LRK-1, a C-elegans PARK8-Related kinase, regulates axonal-dendritic polarity of SV proteins

被引:139
作者
Sakaguchi-Nakashima, Aisa
Meir, James Y.
Jin, Yishi
Matsumoto, Kunihiro [1 ]
Hisamoto, Naoki
机构
[1] Nagoya Univ, Dept Mol Biol, Grad Sch Sci, Inst Adv Res, Nagoya, Aichi 4648602, Japan
[2] Japan Sci & Technol Corp, Solut Oriented Res Sci & Technol, Chikusa Ku, Nagoya, Aichi 4648602, Japan
[3] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA
[4] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA
[5] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA
[6] Univ Calif San Diego, Neurobiol Sect, Div Biol Sci, La Jolla, CA 92093 USA
关键词
D O I
10.1016/j.cub.2007.01.074
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu 1 clathrin adaptor UNC-101, which is involved in polarized dendritic transport, but not on UNC-104 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.
引用
收藏
页码:592 / 598
页数:7
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