LGN regulates mitotic spindle orientation during epithelial morphogenesis

Zheng, Zongheng; Zhu, Huabin; Wan, Qingwen; Liu, Jing; Xiao, Zhuoni; Siderovski, David P.; Du, Quansheng

doi:10.1083/jcb.200910021

Cited by 173 publications

(244 citation statements)

References 55 publications

(98 reference statements)

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“…7A). Orientation of cell division is an early sign of polarization, and previous work has shown that recruitment of a complex comprising NuMA and LGN (also known as GPSM2) to the lateral cortex is required for cell orientation during mitoses in both chick neuroepithelium in vivo and MDCK cells in vitro (Peyre et al, 2011;Zheng et al, 2010). Further, the NuMA-LGN complex recruits Par1b to define lumen position (Lázaro-Diéguez et al, 2013).…”

Section: δU5-gukmentioning

confidence: 99%

“…8A,B). Because previous studies have linked defective mitotic spindle orientation directly to the multi-lumen phenotype (Durgan et al, 2011;Hao et al, 2010;Jaffe et al, 2008;Qin et al, 2010;Rodriguez-Fraticelli et al, 2010;Xia et al, 2015;Zheng et al, 2010), we relied on the strong phenotype of single-versus multi-lumen cyst formation as both a morphogenetic indicator and marker of early polarization processes -e.g. spindle orientation.…”

Section: Full-length But Not Zo-1-binding Defective Occludin Restormentioning

confidence: 99%

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ZO-1 interactions with F-actin and occludin direct epithelial polarization and single lumen specification in 3D culture

Odenwald

Choi

Buckley

et al. 2016

Journal of Cell Science

105

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Epithelia within tubular organs form and expand lumens. Failure of these processes can result in serious developmental anomalies. Although tight junction assembly is crucial to epithelial polarization, the contribution of specific tight junction proteins to lumenogenesis is undefined. Here, we show that ZO-1 (also known as TJP1) is necessary for the formation of single lumens. Epithelia lacking this tight junction scaffolding protein form cysts with multiple lumens and are defective in the earliest phases of polarization, both in two and three dimensions. Expression of ZO-1 domain-deletion mutants demonstrated that the actin-binding region and U5-GuK domain are crucial to single lumen development. For actin-binding region, but not U5-GuK domain, mutants, this could be overcome by strong polarization cues from the extracellular matrix. Analysis of the U5-GuK binding partners shroom2, α-catenin and occludin showed that only occludin deletion led to multi-lumen cysts. Like ZO-1-deficiency, occludin deletion led to mitotic spindle orientation defects. Single lumen formation required the occludin OCEL domain, which binds to ZO-1. We conclude that ZO-1-occludin interactions regulate multiple phases of epithelial polarization by providing cell-intrinsic signals that are required for single lumen formation.

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Section: δU5-gukmentioning

confidence: 99%

Section: Full-length But Not Zo-1-binding Defective Occludin Restormentioning

confidence: 99%

ZO-1 interactions with F-actin and occludin direct epithelial polarization and single lumen specification in 3D culture

Odenwald

Choi

Buckley

et al. 2016

Journal of Cell Science

105

View full text Add to dashboard Cite

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“…Using a quantitative mass-spectrometry approach as a starting point, LIN-5 was found to be phosphorylated by PKC-3; such phosphorylation negatively regulates LIN-5 function and thus contributes to lowering pulling forces on the embryo anterior [50]. In mammalian cells, atypical protein kinase C phosphorylates LGN, causing its loss from the apical cortex in polarized MDCK cells, thereby perturbing spindle positioning [51,52]. Studies in human cells have led to the identification of two other kinases involved in spindle positioning, ABL1 (Abelson kinase1) and PLK1 (Polo-like kinase1).…”

Section: Cortical Dynein: a Force-generating Motormentioning

confidence: 99%

Mechanisms of spindle positioning: cortical force generators in the limelight

Kotak

Gönczy

2013

Current Opinion in Cell Biology

156

138

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Correct positioning of the spindle governs placement of the cytokinesis furrow and thus plays a crucial role in the partitioning of fate determinants and the disposition of daughter cells in a tissue. Converging evidence indicates that spindle positioning is often dictated by interactions between the plus-end of astral microtubules that emanate from the spindle poles and an evolutionary conserved cortical machinery that serves to pull on them. At the heart of this machinery lies a ternary complex (LIN-5/GPR-1/2/Ga in Caenorhabditis elegans and NuMA/LGN/Gai in Homo sapiens) that promotes the presence of the motor protein dynein at the cell cortex. In this review, we discuss how the above components contribute to spindle positioning and how the underlying mechanisms are precisely regulated to ensure the proper execution of this crucial process in metazoan organisms IntroductionThe mitotic spindle is a diamond-shaped microtubulebased structure that faithfully segregates sister chromatids during cell division. Several types of microtubules emanate from the spindle poles, including astral microtubules that reach out to the actin rich cortex located beneath the plasma membrane ( Figure 1a). Pulling forces exerted on the plus-end of astral microtubules at the cell cortex are critical for accurately positioning the spindle with respect to cell-intrinsic or cell-extrinsic spatial cues. In turn, correct spindle positioning dictates placement of the cytokinesis furrow and is thus essential for determining the relative size and spatial disposition of the resulting daughter cells [2]. Accurate spindle positioning also ensures that cell fate determinants are appropriately segregated into daughter cells during development and in stem cell lineages [3].What features of the cell cortex allow interactions with astral microtubules to orchestrate spindle positioning? Specialized cortical sites are key. Their importance has been suggested for instance by elegant experiments in Chaetopterus oocytes, in which the meiotic spindle pulled away from its cortical attachment site using a micro-needle returns to that location once released (Figure 1b). Such experiments illustrate the existence of a mechanical link between the spindle and specialized cortical regions [4,5]. Laser microsurgery experiments in Fusarium solani or C. elegans suggested that this link corresponds to astral microtubules connecting the spindle poles with the cell cortex [6,7,8,9,10 ]. Although not the focus of this review, there are instances where pulling forces are exerted along the length of astral microtubules instead of at their plusend located at the cell cortex [11,12,13]. Work in several systems in recent years has increased our understanding of the basic principles governing spindle positioning and identified core molecular players and aspects of their mechanism of action. In this brief review, we will focus on cortically driven spindle positioning in one-cell C. elegans embryos and mammalian cells in culture. In doing so, we will discuss the nature of the t...

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“…The Gai complex also partakes in planar epithelial divisions of epithelial monolayers. [47][48][49] In this case, the Gai complex recruits Dynein-dynactin to the lateral cortex, which pull spindle poles toward the lateral side of the dividing cells. In certain cell types aPKC plays an active role excluding LGN from the apical domain and restricting it to the lateral cortex.…”

Section: Cell Polarity and Polarized Cell Divisionsmentioning

confidence: 99%