LGN/mInsc and LGN/NuMA Complex Structures Suggest Distinct Functions in Asymmetric Cell Division for the Par3/mInsc/LGN and Gαi/LGN/NuMA Pathways

Jinwei Zhu; Wenyu Wen; Zhen Zheng; Yuan Shang; Zhiyi Wei; Zhuoni Xiao; Zhu Pan; Quansheng Du; Wenning Wang; Mingjie Zhang

doi:10.1016/j.molcel.2011.07.011

LGN/mInsc and LGN/NuMA Complex Structures Suggest Distinct Functions in Asymmetric Cell Division for the Par3/mInsc/LGN and Gαi/LGN/NuMA Pathways

Jinwei Zhu, Wenyu Wen, Zhen Zheng, Yuan Shang, Zhiyi Wei, Zhuoni Xiao, Zhu Pan, Quansheng Du, Wenning Wang, Mingjie Zhang

Research output: Contribution to journal › Article › peer-review

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Abstract

Asymmetric cell division requires the establishment of cortical cell polarity and the orientation of the mitotic spindle along the axis of cell polarity. Evidence from invertebrates demonstrates that the Par3/Par6/aPKC and NuMA/LGN/G. αi complexes, which are thought to be physically linked by the adaptor protein mInscuteable (mInsc), play indispensable roles in this process. However, the molecular basis for the binding of LGN to NuMA and mInsc is poorly understood. The high-resolution structures of the LGN/NuMA and LGN/mInsc complexes presented here provide mechanistic insights into the distinct and highly specific interactions of the LGN TPRs with mInsc and NuMA. Structural comparisons, together with biochemical and cell biology studies, demonstrate that the interactions of NuMA and mInsc with LGN are mutually exclusive, with mInsc binding preferentially. Our results suggest that the Par3/mInsc/LGN and NuMA/LGN/Gαi complexes play sequential and partially overlapping roles in asymmetric cell division.

Original language	English (US)
Pages (from-to)	418-431
Number of pages	14
Journal	Molecular Cell
Volume	43
Issue number	3
DOIs	https://doi.org/10.1016/j.molcel.2011.07.011
State	Published - Aug 5 2011

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2011.07.011

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@article{db76a5e2e78f4d0ebc292c3458647bcf,

title = "LGN/mInsc and LGN/NuMA Complex Structures Suggest Distinct Functions in Asymmetric Cell Division for the Par3/mInsc/LGN and Gαi/LGN/NuMA Pathways",

abstract = "Asymmetric cell division requires the establishment of cortical cell polarity and the orientation of the mitotic spindle along the axis of cell polarity. Evidence from invertebrates demonstrates that the Par3/Par6/aPKC and NuMA/LGN/G. αi complexes, which are thought to be physically linked by the adaptor protein mInscuteable (mInsc), play indispensable roles in this process. However, the molecular basis for the binding of LGN to NuMA and mInsc is poorly understood. The high-resolution structures of the LGN/NuMA and LGN/mInsc complexes presented here provide mechanistic insights into the distinct and highly specific interactions of the LGN TPRs with mInsc and NuMA. Structural comparisons, together with biochemical and cell biology studies, demonstrate that the interactions of NuMA and mInsc with LGN are mutually exclusive, with mInsc binding preferentially. Our results suggest that the Par3/mInsc/LGN and NuMA/LGN/Gαi complexes play sequential and partially overlapping roles in asymmetric cell division.",

author = "Jinwei Zhu and Wenyu Wen and Zhen Zheng and Yuan Shang and Zhiyi Wei and Zhuoni Xiao and Zhu Pan and Quansheng Du and Wenning Wang and Mingjie Zhang",

note = "Funding Information: We thank Anthony Zhang for editing the manuscript, Duane Compton for the anti-NuMA antibody, and the Shanghai Synchrotron Radiation Facility BL17U for X-ray beam time. This work was supported by the National High Technology Research Program (2006AA02A320), the National Major Basic Research Program (2009CB918600, 2011CB808505), National Science Foundation of China (30970574, 20973040, 31070642), the Shanghai Rising-Star Program (10QA1400700), Science and Technology Commission of Shanghai Municipality (08DZ2270500), Shanghai Leading Academic Discipline Project (B108) to W. Wen and W. Wang, National Institute of Health grant (GM079506) and American Cancer Society grant (RSG0717601CSM) to Q.D., and RGC grants (663808, 664009, 660709, 663610, HKUST6/CRF/10, SEG_HKUST06, AoE/B-15/01-II, and AoE/M-04/04) to M.Z. ",

year = "2011",

month = aug,

day = "5",

doi = "10.1016/j.molcel.2011.07.011",

language = "English (US)",

volume = "43",

pages = "418--431",

journal = "Molecular Cell",

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TY - JOUR

T1 - LGN/mInsc and LGN/NuMA Complex Structures Suggest Distinct Functions in Asymmetric Cell Division for the Par3/mInsc/LGN and Gαi/LGN/NuMA Pathways

AU - Zhu, Jinwei

AU - Wen, Wenyu

AU - Zheng, Zhen

AU - Shang, Yuan

AU - Wei, Zhiyi

AU - Xiao, Zhuoni

AU - Pan, Zhu

AU - Du, Quansheng

AU - Wang, Wenning

AU - Zhang, Mingjie

N1 - Funding Information: We thank Anthony Zhang for editing the manuscript, Duane Compton for the anti-NuMA antibody, and the Shanghai Synchrotron Radiation Facility BL17U for X-ray beam time. This work was supported by the National High Technology Research Program (2006AA02A320), the National Major Basic Research Program (2009CB918600, 2011CB808505), National Science Foundation of China (30970574, 20973040, 31070642), the Shanghai Rising-Star Program (10QA1400700), Science and Technology Commission of Shanghai Municipality (08DZ2270500), Shanghai Leading Academic Discipline Project (B108) to W. Wen and W. Wang, National Institute of Health grant (GM079506) and American Cancer Society grant (RSG0717601CSM) to Q.D., and RGC grants (663808, 664009, 660709, 663610, HKUST6/CRF/10, SEG_HKUST06, AoE/B-15/01-II, and AoE/M-04/04) to M.Z.

PY - 2011/8/5

Y1 - 2011/8/5

N2 - Asymmetric cell division requires the establishment of cortical cell polarity and the orientation of the mitotic spindle along the axis of cell polarity. Evidence from invertebrates demonstrates that the Par3/Par6/aPKC and NuMA/LGN/G. αi complexes, which are thought to be physically linked by the adaptor protein mInscuteable (mInsc), play indispensable roles in this process. However, the molecular basis for the binding of LGN to NuMA and mInsc is poorly understood. The high-resolution structures of the LGN/NuMA and LGN/mInsc complexes presented here provide mechanistic insights into the distinct and highly specific interactions of the LGN TPRs with mInsc and NuMA. Structural comparisons, together with biochemical and cell biology studies, demonstrate that the interactions of NuMA and mInsc with LGN are mutually exclusive, with mInsc binding preferentially. Our results suggest that the Par3/mInsc/LGN and NuMA/LGN/Gαi complexes play sequential and partially overlapping roles in asymmetric cell division.

AB - Asymmetric cell division requires the establishment of cortical cell polarity and the orientation of the mitotic spindle along the axis of cell polarity. Evidence from invertebrates demonstrates that the Par3/Par6/aPKC and NuMA/LGN/G. αi complexes, which are thought to be physically linked by the adaptor protein mInscuteable (mInsc), play indispensable roles in this process. However, the molecular basis for the binding of LGN to NuMA and mInsc is poorly understood. The high-resolution structures of the LGN/NuMA and LGN/mInsc complexes presented here provide mechanistic insights into the distinct and highly specific interactions of the LGN TPRs with mInsc and NuMA. Structural comparisons, together with biochemical and cell biology studies, demonstrate that the interactions of NuMA and mInsc with LGN are mutually exclusive, with mInsc binding preferentially. Our results suggest that the Par3/mInsc/LGN and NuMA/LGN/Gαi complexes play sequential and partially overlapping roles in asymmetric cell division.

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DO - 10.1016/j.molcel.2011.07.011

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AN - SCOPUS:79960913555

SN - 1097-2765

VL - 43

SP - 418

EP - 431

JO - Molecular Cell

JF - Molecular Cell

IS - 3

ER -

LGN/mInsc and LGN/NuMA Complex Structures Suggest Distinct Functions in Asymmetric Cell Division for the Par3/mInsc/LGN and Gαi/LGN/NuMA Pathways

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