RT Journal Article
SR Electronic
T1 Dynactin has two antagonistic regulatory domains and exerts opposing effects on dynein motility
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 110775
DO 10.1101/110775
A1 Takuya Kobayashi
A1 Takuya Miyashita
A1 Takashi Murayama
A1 Yoko Y. Toyoshima
YR 2017
UL http://biorxiv.org/content/early/2017/02/24/110775.abstract
AB Dynactin is a dynein-regulating protein that increases the processivity of dynein movement on microtubules. Recent studies have shown that a tripartite complex of dynein–dynactin–Bicaudal D2 is essential for highly processive movement. To elucidate the regulation of dynein motility by dynactin, we focused on two isoforms (A and B) of dynactin 1 (DCTN1), the largest subunit of dynactin that contains both microtubule- and dynein-binding domains. The only difference between the primary structures of the two isoforms is that DCTN1B lacks the K-rich domain, a cluster of basic residues. We measured dynein motility by single molecule observation of recombinant dynein and dynactin. Whereas the tripartite complex containing DCTN1A exhibited highly processive movement, the complex containing DCTN1B dissociated from microtubules with no apparent processive movement. This inhibitory effect of DCTN1B was caused by reductions of the microtubule-binding affinities of both dynein and dynactin, which is attributed to the coiled-coil 1 domain of DCTN1. In DCTN1A, the K-rich domain antagonized these inhibitory effects. Therefore, dynactin has two antagonistic domains and promotes or suppresses dynein motility to accomplish correct localization and functions of dynein within a cell.