TY - JOUR
T1 - Nudel/NudE and Lis1 promote dynein and dynactin interaction in the context of spindle morphogenesis
AU - Wang, Shusheng
AU - Ketcham, Stephanie A.
AU - Schön, Arne
AU - Goodman, Benjamin
AU - Wang, Yueju
AU - Yates, John
AU - Freire, Ernesto
AU - Schroer, Trina A.
AU - Zheng, Yixian
PY - 2013/11/15
Y1 - 2013/11/15
N2 - Lis1, Nudel/NudE, and dynactin are regulators of cytoplasmic dynein, a minus end-directed, microtubule (MT)-based motor required for proper spindle assembly and orientation. In vitro studies have shown that dynactin promotes processive movement of dynein on MTs, whereas Lis1 causes dynein to enter a persistent force-generating state (referred to here as dynein stall). Yet how the activities of Lis1, Nudel/NudE, and dynactin are coordinated to regulate dynein remains poorly understood in vivo. Working in Xenopus egg extracts, we show that Nudel/NudE facilitates the binding of Lis1 to dynein, which enhances the recruitment of dynactin to dynein. We further report a novel Lis1-dependent dynein-dynactin interaction that is essential for the organization of mitotic spindle poles. Finally, using assays for MT gliding and spindle assembly, we demonstrate an antagonistic relationship between Lis1 and dynactin that allows dynactin to relieve Lis1-induced dynein stall on MTs. Our findings suggest the interesting possibility that Lis1 and dynactin could alternately engage with dynein to allow the motor to promote spindle assembly.
AB - Lis1, Nudel/NudE, and dynactin are regulators of cytoplasmic dynein, a minus end-directed, microtubule (MT)-based motor required for proper spindle assembly and orientation. In vitro studies have shown that dynactin promotes processive movement of dynein on MTs, whereas Lis1 causes dynein to enter a persistent force-generating state (referred to here as dynein stall). Yet how the activities of Lis1, Nudel/NudE, and dynactin are coordinated to regulate dynein remains poorly understood in vivo. Working in Xenopus egg extracts, we show that Nudel/NudE facilitates the binding of Lis1 to dynein, which enhances the recruitment of dynactin to dynein. We further report a novel Lis1-dependent dynein-dynactin interaction that is essential for the organization of mitotic spindle poles. Finally, using assays for MT gliding and spindle assembly, we demonstrate an antagonistic relationship between Lis1 and dynactin that allows dynactin to relieve Lis1-induced dynein stall on MTs. Our findings suggest the interesting possibility that Lis1 and dynactin could alternately engage with dynein to allow the motor to promote spindle assembly.
UR - http://www.scopus.com/inward/record.url?scp=84888271452&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888271452&partnerID=8YFLogxK
U2 - 10.1091/mbc.E13-05-0283
DO - 10.1091/mbc.E13-05-0283
M3 - Article
C2 - 24025714
AN - SCOPUS:84888271452
SN - 1059-1524
VL - 24
SP - 3522
EP - 3533
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 22
ER -