Mammalian Lgl Forms a Protein Complex with PAR-6 and aPKC Independently of PAR-3 to Regulate Epithelial Cell Polarity

Yamanaka, Tatsuhiko; Horikoshi, Yosuke; Sugiyama, Yuki; Ishiyama, Chikako; Suzuki, Atsushi; Hirose, Tomonori; Iwamatsu, Akihiro; Shinohara, Azusa; Ohno, Shigeo

doi:10.1016/s0960-9822(03)00244-6

Cited by 321 publications

(378 citation statements)

References 42 publications

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“…Earlier studies have demonstrated that the several closely spaced, highly conserved phosphorylation sites in the central linker region of Lgl2 can be phosphorylated by aPKC both in vivo and in vitro [16][17][18][19] (Figure 1A). Although phosphorylation is believed to be important for the proper function of Lgl2, how the phosphorylation of Lgl2 affects its function is still unclear.…”

Section: The Phosphorylation-dependent Interaction Between Lgl2 and Dmentioning

confidence: 91%

Phosphorylation-dependent interaction between tumor suppressors Dlg and Lgl

et al. 2014

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Section: The Phosphorylation-dependent Interaction Between Lgl2 and Dmentioning

confidence: 91%

Phosphorylation-dependent interaction between tumor suppressors Dlg and Lgl

et al. 2014

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“…Par3, Par6, and aPKC form an apical protein complex (reviewed in Etienne- Manneville and Hall, 2003). Formation of this complex controls microtubule organization and excludes basolateral proteins, such as Lethal giant larvae (Lgl), from the apical membrane by direct aPKC-mediated phosphorylation (Plant et al, 2003;Yamanaka et al, 2003). Disruption of the apical protein complex or inhibition of aPKC function prevents formation of a functional apical domain and ultimately disrupts apical/ basal polarity.…”

Section: Molecular Regulation Of Te Vs Icm Fate Choicementioning

confidence: 99%

Cell and molecular regulation of the mouse blastocyst

Yamanaka

Ralston

Stephenson

et al. 2006

Developmental Dynamics

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Animals use diverse strategies to specify tissue lineages during development. A common strategy is to partition maternally supplied and localized lineage determinants into progenitor cells. The mouse embryo appears to use a different, more regulative strategy to specify the first three lineages: the epiblast (EPI: future embryo), the trophectoderm (TE: future placenta), and the primitive endoderm (PE: future yolk sac). These lineages are specified during two successive differentiation steps leading to formation of the blastocyst. Here, we review classic and contemporary models of early lineage specification in the mouse, and describe recent efforts to understand the molecular regulation of these events. We describe evidence that trophectoderm differentiation bears resemblance to the process of epithelialization and describe the importance of apical/basal protein complexes in regulating this process. Next, we present a revised model of PE specification, and describe evidence that PE cells in the inner cell mass sort out to occupy their ultimate position on the surface of the EPI. Finally, we describe factors that reinforce these lineages and three distinct stem cell types that can be isolated from them. Together, these mechanisms guide the differentiation of the first lineages of the mouse and thereby set up tissues that will be important for the first steps of embryonic body patterning. Developmental Dynamics 235:2301-2314, 2006.

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“…Although it is possible that NMHC II-B serves as a downstream target of aPKC in regulating cell adhesion in the spinal canal, there are other putative targets in the neuronal adherens junction as well, such as PAR3 and Lgl1 (Yamanaka et al, 2003;Klezovitch et al, 2004;Suzuki and Ohno, 2006;Vasioukhin, 2006). In contrast, Even-Faitelson and Ravid (2006) have reported that phosphorylation of the NMHC II-B in the nonhelical tail by an aPKC results in cortical localization of both NM II-B and aPKC in a prostate cancer cell line.…”

Section: Cell-cell Adhesion Of the Neuroepithelial Cells Requires Nonmentioning

confidence: 99%

Loss of Cell Adhesion Causes Hydrocephalus in Nonmuscle Myosin II-B–ablated and Mutated Mice

Bao

Adelstein

2007

MBoC

103

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Ablation of nonmuscle myosin (NM) II-B in mice during embryonic development leads to marked enlargement of the cerebral ventricles and destruction of brain tissue, due to hydrocephalus. We have identified a transient mesh-like structure present at the apical border of cells lining the spinal canal of mice during development. This structure, which only contains the II-B isoform of NM, also contains ␤-catenin and N-cadherin, consistent with a role in cell adhesion. Ablation of NM II-B or replacement of NM II-B with decreased amounts of a mutant (R709C), motor-impaired NM II-B in mice results in collapse of the mesh-like structure and loss of cell adhesion. This permits the underlying neuroepithelial cells to invade the spinal canal and obstruct cerebral spinal fluid flow. These defects in the CNS of NM II-B-ablated mice seem to be the cause of hydrocephalus. Interestingly, the mesh-like structure and patency of the spinal canal can be restored by increasing expression of the motor-impaired NM II-B, which also rescues hydrocephalus. However, the mutant isoform cannot completely rescue neuronal cell migration. These studies show that the scaffolding properties of NM II-B play an important role in cell adhesion, thereby preventing hydrocephalus during mouse brain development. INTRODUCTIONCongenital hydrocephalus affects one to three humans per 1000 live births. The results of this abnormality can be devastating in that severe, untreated hydrocephalus can destroy brain tissue and thereby lead to mental retardation. Hydrocephalus occurs when there is an increase in pressure in the ventricular chambers due to a blockage in the circulation of cerebral spinal fluid (CSF) or when there is an increase in production or decrease in the absorption of the CSF. The defect may be accompanied by an obstructed aqueduct of Sylvius, the narrow channel connecting the third and fourth brain ventricles (noncommunicating hydrocephalus), or by a normal aqueduct (communicating hydrocephalus). The pathogenesis of most cases of communicating hydrocephalus is largely unknown (for reviews, see Perez-Figares et al., 2001;Crews et al., 2004).Nonmuscle myosin (NM) II, one of the major cytoskeletal motor proteins, plays an important role in cell migration (Svitkina et al., 1997;Ma et al., 2004;Even-Ram et al., 2007;Vicente-Manzanares et al., 2007), cell-cell adhesion Shewan et al., 2005;Giannone et al., 2007), and cell division (De Lozanne and Spudich, 1987;Takeda et al., 2003;Bao et al., 2005). The molecular structure of NM II is a hexamer consisting of a pair of myosin heavy chains (200 kDa) and two pairs of light chains (20 and 17 kDa). In mammals, three isoforms of the nonmuscle myosin heavy chain (NMHC) have been identified, NMHC II-A, II-B, and II-C, encoded by three different genes, Myh 9, Myh 10, and Myh 14 in humans. The NMHCs share a 60 -80% identity in amino acids, but they show significant differences in their motor activities (Golomb et al., 2004;Kim et al., 2005). In general, all three isoforms are ubiquitously expressed in vertebrat...

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Mammalian Lgl Forms a Protein Complex with PAR-6 and aPKC Independently of PAR-3 to Regulate Epithelial Cell Polarity

Abstract: These results indicate that PAR-6/aPKC selectively interacts with either mLgl or PAR-3 under the control of aPKC activity to regulate epithelial cell polarity.

Cited by 321 publications

References 42 publications

Phosphorylation-dependent interaction between tumor suppressors Dlg and Lgl

Phosphorylation-dependent interaction between tumor suppressors Dlg and Lgl

Cell and molecular regulation of the mouse blastocyst

Loss of Cell Adhesion Causes Hydrocephalus in Nonmuscle Myosin II-B–ablated and Mutated Mice

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