Comparative analysis of two Caenorhabditis elegans kinesins KLP-6 and UNC-104 reveals a common and distinct activation mechanism in kinesin-3

被引:5
|
作者
Kita, Tomoki [1 ]
Chiba, Kyoko [2 ]
Wang, Jiye [3 ]
Nakagawa, Atsushi [3 ]
Niwa, Shinsuke [1 ,2 ]
机构
[1] Tohoku Univ, Grad Sch Life Sci, Sendai, Japan
[2] Tohoku Univ, Frontier Res Inst Interdisciplinary Sci FRIS, Sendai, Japan
[3] Osaka Univ, Inst Prot Res, Osaka, Japan
来源
ELIFE | 2024年 / 12卷
基金
日本学术振兴会;
关键词
kinesin; KIF1A; UNC-104; KLP-6; axonal transport; intraflagellar transport; kinesin-3; C; elegans; POLYCYSTIC KIDNEY-DISEASE; AXONAL-TRANSPORT; MONOMERIC MOTOR; GENE ENCODES; PROTEIN; DOMAIN; KIF1A;
D O I
10.7554/eLife.89040
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Kinesin-3 is a family of microtubule-dependent motor proteins that transport various cargos within the cell. However, the mechanism underlying kinesin-3 activations remains largely elusive. In this study, we compared the biochemical properties of two Caenorhabditis elegans kinesin-3 family proteins, KLP-6 and UNC-104. Both KLP-6 and UNC-104 are predominantly monomeric in solution. As previously shown for UNC-104, non-processive KLP-6 monomer is converted to a processive motor when artificially dimerized. We present evidence that releasing the autoinhibition is sufficient to trigger dimerization of monomeric UNC-104 at nanomolar concentrations, which results in processive movement of UNC-104 on microtubules, although it has long been thought that enrichment in the phospholipid microdomain on cargo vesicles is required for the dimerization and processive movement of UNC-104. In contrast, KLP-6 remains to be a non-processive monomer even when its autoinhibition is unlocked, suggesting a requirement of other factors for full activation. By examining the differences between KLP-6 and UNC-104, we identified a coiled-coil domain called coiled-coil 2 (CC2) that is required for the efficient dimerization and processive movement of UNC-104. Our results suggest a common activation mechanism for kinesin-3 family members, while also highlighting their diversification.
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页数:20
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