TY - JOUR
T1 - Rab11 Endosomes Contribute to Mitotic Spindle Organization and Orientation
AU - Hehnly, Heidi
AU - Doxsey, Stephen
N1 - Funding Information:
This work was supported by National Institutes of Health (NIH) grants GM051994 (to S.D.) and K99GM107355 (to H.H.). We are grateful to Alison Bright, Chun-Ting Chen (Doxsey laboratory), Felix Rivera-Molina, and Derek Toomre (Yale) for their revisions to this manuscript. We thank Mark Stamnes (University of Iowa) for his advice and assistance in the MT membrane in vitro reassembly experiments. We thank Dr. Paul Furcinitti of the Digital Light Microscopy Core Facility at the University of Massachusetts Medical School for assistance with live-cell spinning disk confocal microscopy.
PY - 2014/3/10
Y1 - 2014/3/10
N2 - During interphase, Rab11-GTPase-containing endosomes recycle endocytic cargo. However, little is known about Rab11 endosomes in mitosis. Here, we show that Rab11 localizes to the mitotic spindle and regulates dynein-dependent endosome localization at poles. We found that mitotic recycling endosomes bind γ-TuRC components and associate with tubulin invitro. Rab11 depletion or dominant-negative Rab11 expression disrupts astral microtubules, delays mitosis, and redistributes spindle pole proteins. Reciprocally, constitutively active Rab11 increases astral microtubules, restores γ-tubulin spindle pole localization, and generates robust spindles. This suggests a role for Rab11 activity in spindle pole maturation during mitosis. Rab11 depletion causes misorientation of the mitotic spindle and the plane of cell division. These findings suggest a molecular mechanism for the organization of astral microtubules and the mitotic spindle through Rab11-dependent control of spindle pole assembly and function. We propose that Rab11 and its associated endosomes cocontribute to these processes through retrograde transport to poles by dynein.
AB - During interphase, Rab11-GTPase-containing endosomes recycle endocytic cargo. However, little is known about Rab11 endosomes in mitosis. Here, we show that Rab11 localizes to the mitotic spindle and regulates dynein-dependent endosome localization at poles. We found that mitotic recycling endosomes bind γ-TuRC components and associate with tubulin invitro. Rab11 depletion or dominant-negative Rab11 expression disrupts astral microtubules, delays mitosis, and redistributes spindle pole proteins. Reciprocally, constitutively active Rab11 increases astral microtubules, restores γ-tubulin spindle pole localization, and generates robust spindles. This suggests a role for Rab11 activity in spindle pole maturation during mitosis. Rab11 depletion causes misorientation of the mitotic spindle and the plane of cell division. These findings suggest a molecular mechanism for the organization of astral microtubules and the mitotic spindle through Rab11-dependent control of spindle pole assembly and function. We propose that Rab11 and its associated endosomes cocontribute to these processes through retrograde transport to poles by dynein.
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U2 - 10.1016/j.devcel.2014.01.014
DO - 10.1016/j.devcel.2014.01.014
M3 - Article
C2 - 24561039
AN - SCOPUS:84896691702
VL - 28
SP - 497
EP - 507
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 5
ER -