Mutually Exclusive Cytoplasmic Dynein Regulation by NudE-Lis1 and Dynactin

Abstract

Background: Cytoplasmic dynein performs a great variety of cellular functions using a diversity of regulators. Results: NudE and dynactin compete for a common site within the dynein complex. Conclusion: This mechanism prevents dual regulation by dynactin and LIS1 and suggests a major new mode of regulatory control. Significance: This is the first insight into coordination of cytoplasmic dynein regulators.

Dynein Regulators Are Important for Ecotropic Murine Leukemia Virus Infection

“…Considering that dynactin interacts with the dynein complex via p150 and Dync1i2 and that NudEL also directly interacts with the dynein intermediate chain (41,42), we can attribute the 50% reduction of MLV infection in Dync1i2 KD cells to disruption of this interaction. It is possible that in Dync1i2 KD cells the quantities of dynein-dynactin and dynein-NudEL are reduced and that this affects the probability of virus attachment to the motor complex.…”

Arl3 and LC8 regulate dissociation of dynactin from dynein

“…1c,d). Functional importance of this domain to binding with dynein DIC is controversial [11][12][13] . The mechanisms by which Arl3 binding to p150 Glued facilitates the disassembly of dynein-dynactin complex is unknown.…”

“…The second coiled-coil domain of p150 Glued aa 925-1050 on coiled coil 2 (CC2) contains a conserved actin-binding motif that has been proposed to bind the Arp1 filament directly 10 . Moreover, p150 Glued aa 217-548 on CC1 interacts with amino-terminal fragments of the dynein IC (DIC) 11 and the aa 600-811 was also reported to bind full-length DIC 12 , but the latter binding is controversial 13 . Thus, p150 Glued functions as a hub for connection of dynein with cargo.…”

Functional coupling of microtubules to membranes – implications for membrane structure and dynamics

“…Thus, NDE1 and LIS1 appear to act together to generate a dynein complex that is capable of moving heavy loads, whereas dynactin acts to enhance processivity. This is strongly supported by the fact that LIS1 and dynactin appear to bind to dynein in a mutually exclusive manner (McKenney et al, 2011).…”