BicD and MAP7 Collaborate to Activate Homodimeric Drosophila Kinesin-1 by Complementary Mechanisms.

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Tác giả: M Yusuf Ali, Patricia M Fagnant, Hailong Lu, Jill E Macfarlane, Kathleen M Trybus

Ngôn ngữ: eng

Ký hiệu phân loại: 629.2272 Motor land vehicles, cycles

Thông tin xuất bản: England : Traffic (Copenhagen, Denmark) , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 746625

The folded auto-inhibited state of kinesin-1 is stabilized by multiple weak interactions and binds poorly to microtubules. Here we investigate the extent to which homodimeric Drosophila kinesin-1 lacking light chains is activated by the dynein activating adaptor Drosophila BicD. We show that one or two kinesins can bind to the central region of BicD (CC2), a region distinct from that which binds dynein-dynactin (CC1) and cargo-adaptor proteins (CC3). Kinesin light chain significantly reduces the amount of kinesin bound to BicD and thus regulates this interaction. Binding of BicD to kinesin enhances processive motion, suggesting that the adaptor relieves kinesin auto-inhibition. In contrast, the kinesin-binding domain of microtubule-associated protein 7 (MAP7) has minimal impact on the fraction of motors moving processively while full-length MAP7 enhances kinesin-1 recruitment to the microtubule and run length because of its microtubule-binding domain. BicD thus relieves auto-inhibition of kinesin, while MAP7 enhances motor engagement with the microtubules. When BicD and MAP7 are combined, the most robust activation of kinesin-1 occurs, highlighting the crosstalk between adaptors and microtubule-associated proteins in regulating transport.
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