共 59 条
Emerin organizes actin flow for nuclear movement and centrosome orientation in migrating fibroblasts
被引:68
作者:
Chang, Wakam
[1
]
Folker, Eric S.
[1
]
Worman, Howard J.
[1
,2
]
Gundersen, Gregg G.
[1
]
机构:
[1] Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY 10032 USA
[2] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA
基金:
美国国家卫生研究院;
关键词:
DREIFUSS MUSCULAR-DYSTROPHY;
NONMUSCLE MYOSIN-II;
F-ACTIN;
NEURONAL MIGRATION;
ENVELOPE INTEGRITY;
CELL-ADHESION;
LINC COMPLEX;
TAN LINES;
MEMBRANE;
DYNAMICS;
D O I:
10.1091/mbc.E13-06-0307
中图分类号:
Q2 [细胞生物学];
学科分类号:
071009 ;
090102 ;
摘要:
In migrating fibroblasts, rearward movement of the nucleus orients the centrosome toward the leading edge. Nuclear movement results from coupling rearward-moving, dorsal actin cables to the nucleus by linear arrays of nesprin-2G and SUN2, termed transmembrane actin-associated nuclear (TAN) lines. A-type lamins anchor TAN lines, prompting us to test whether emerin, a nuclear membrane protein that interacts with lamins and TAN line proteins, contributes to nuclear movement. In fibroblasts depleted of emerin, nuclei moved nondirectionally or completely failed to move. Consistent with these nuclear movement defects, dorsal actin cable flow was nondirectional in cells lacking emerin. TAN lines formed normally in cells lacking emerin and were coordinated with the erratic nuclear movements, although in 20% of the cases, TAN lines slipped over immobile nuclei. Myosin II drives actin flow, and depletion of myosin IIB, but not myosin IIA, showed similar nondirectional nuclear movement and actin flow as in emerin-depleted cells. Myosin IIB specifically coimmunoprecipitated with emerin, and emerin depletion prevented myosin IIB localization near nuclei. These results show that emerin functions with myosin IIB to polarize actin flow and nuclear movement in fibroblasts, suggesting a novel function for the nuclear envelope in organizing directional actin flow and cytoplasmic polarity.
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页码:3869 / 3880
页数:12
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