PT  - JOURNAL ARTICLE
AU  - Thomas E. Sladewski
AU  - Neil Billington
AU  - M. Yusuf Ali
AU  - Carol S. Bookwalter
AU  - Hailong Lu
AU  - Elena B. Krementsova
AU  - Trina A. Schroer
AU  - Kathleen M. Trybus
TI  - Recruitment of Two Dyneins to an mRNA-Dependent Bicaudal D Transport Complex
AID  - 10.1101/273755
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 273755
4099  - http://biorxiv.org/content/early/2018/02/28/273755.short
4100  - http://biorxiv.org/content/early/2018/02/28/273755.full
AB  - We investigated the role of binding partners of full-length Drosophila Bicaudal D (BicD) in the activation of dynein-dynactin motility for mRNA transport on microtubules. In single-molecule assays, full-length BicD robustly activated dynein-dynactin only when both the mRNA binding protein Egalitarian (Egl), and K10 mRNA cargo were present. Electron microscopy showed that both Egl and mRNA were needed to disrupt an auto-inhibited, looped BicD conformation that sterically prevents dynein-dynactin binding. In vitro reconstituted messenger ribonucleoprotein (mRNP) complexes with two Egl molecules showed faster speeds and longer run lengths than mRNPs with one Egl, suggesting that cargo binding enhances dynein recruitment. Labeled dynein showed that BicD can recruit two dimeric dyneins to the mRNP, resulting in faster speeds and longer run lengths than with one dynein. The fully reconstituted mRNP provides a model for understanding how adaptor proteins and cargo cooperate to confer optimal transport properties to a dynein-driven transport complex.