Rab6, Rab8, and MICAL3 Cooperate in Controlling Docking and Fusion of Exocytotic Carriers

Grigoriev, Ilya; Yu, Ka Lou; Martinez-Sanchez, Emma; Serra-Marques, Andrea; Smal, Ihor; Meijering, Erik; Demmers, Jeroen; Peränen, Johan; Pasterkamp, R. Jeroen; Sluijs, Peter van der; Hoogenraad, Casper C.; Akhmanova, Anna

doi:10.1016/j.cub.2011.04.030

Cited by 177 publications

(297 citation statements)

References 31 publications

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“…Other components of the same cortical assembly are the scaffolding proteins liprin-a1 and b1, a coiled-coil adaptor ELKS/ERC1, and the kinesin-4 KIF21A (Lansbergen et al, 2006;van der Vaart et al, 2013). Both liprins and ELKS are best known for their role in organizing presynaptic secretory sites (Hida and Ohtsuka, 2010;Spangler and Hoogenraad, 2007); in agreement with this function, ELKS is required for efficient constitutive exocytosis in HeLa cells (Grigoriev et al, 2007(Grigoriev et al, , 2011. LL5b, liprins and ELKS form micrometer-sized cortical patch-like structures, which will be termed here cortical microtubule stabilization complexes, or CMSCs.…”

Section: Introductionmentioning

confidence: 93%

Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions

Bouchet

Gough

Willige

et al. 2016

Preprint

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108

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The cross-talk between dynamic microtubules and integrin-based adhesions to the extracellular matrix plays a crucial role in cell polarity and migration. Microtubules regulate the turnover of adhesion sites, and, in turn, focal adhesions promote the cortical microtubule capture and stabilization in their vicinity, but the underlying mechanism is unknown. Here, we show that cortical microtubule stabilization sites containing CLASPs, KIF21A, LL5b and liprins are recruited to focal adhesions by the adaptor protein KANK1, which directly interacts with the major adhesion component, talin. Structural studies showed that the conserved KN domain in KANK1 binds to the talin rod domain R7. Perturbation of this interaction, including a single point mutation in talin, which disrupts KANK1 binding but not the talin function in adhesion, abrogates the association of microtubule-stabilizing complexes with focal adhesions. We propose that the talin-KANK1 interaction links the two macromolecular assemblies that control cortical attachment of actin fibers and microtubules.

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Section: Introductionmentioning

confidence: 93%

Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions

Bouchet

Gough

Willige

et al. 2016

Preprint

Self Cite

108

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“…45 Rab6 controls the budding and motility of exocytic vesicles, 46 and mediates the recruitment of Rab8, which controls docking and fusion. 47 Thus Rab6 and 8 may act in concert to deliver newly synthesized TRP channels to the plasma membrane from the Golgi. However, given how quickly calcium fluxes increase at the plasma membrane following HGF stimulation, 31 channel recycling better accounts for the timing of high frequency plasma membrane calcium fluxes than delivery of newly synthesized TRP channels.…”

Section: Molecular Control Of Calcium Influxes Upon Induction Of Epitmentioning

confidence: 99%

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

2016

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Epithelial tissues use adherens junctions to maintain tight interactions and coordinate cellular activities. Adherens junctions are remodeled during epithelial morphogenesis, including instances of epithelialmesenchymal transition, or EMT, wherein individual cells detach from the tissue and migrate as individual cells. EMT has been recapitulated by growth factor induction of epithelial scattering in cell culture. In culture systems, cells undergo a highly reproducible series of cell morphology changes, most notably cell spreading followed by cellular compaction and cell migration. These morphology changes are accompanied by striking actin rearrangements. The current evidence suggests that global changes in actomyosin-based cellular contractility, first a loss of contractility during spreading and its activation during cell compaction, are the main drivers of epithelial scattering. In this review, we focus on how spreading and contractility might be controlled during epithelial scattering. While we propose a central role for RhoA, which is well known to control cellular contractility in multiple systems and whose role in epithelial scattering is well accepted, we suggest potential roles for additional cellular systems whose role in epithelial cell biology has been less well documented. In particular, we propose critical roles for vesicle recycling, calcium channels, and calcium-dependent kinases.

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“…The gene for miR-648 is located in the first intron of MICAL3, encoding a member of the MICAL family of flavoprotein monooxygenases, implicated in axon guidance and actin remodeling (35,36). More recently, MICAL3 has been shown to cooperate with Rab6 and Rab8 in exocytosis events (29). The orientation and location of the miR-648 gene indicates that it is transcribed from the same DNA template strand as MICAL3, thus it is likely that pre-miR-648 is within a MICAL3 transcription unit (Fig.…”

Section: Posttranscriptional Regulation Ofmentioning

confidence: 99%

“…Here, we show that the level of microRNA 648 (miR-648), having a seed sequence complementary to the 3= untranslated region (UTR) of ET-1 mRNA, was attenuated in response to treatment of cultured endothelial cells with PlGF. Moreover, we show that miR-648 located in a 5=-proximal intron of the MICAL3 gene (i.e., the microtubule-associated monooxygenase, calponin, and LIM domain containing 3 gene), a member of the MICAL family of flavoprotein monooxygenases (29), is cotranscribed with MICAL3 pre-mRNA and undergoes maturation following excision of the intron containing pre-miR-648. In addition, our studies show for the first time, to the best of our knowledge, that PAX5 (paired box protein 5) transcriptionally activates coexpression of MICAL3 and pre-miR-648 in human endothelial cells and that the 3= UTR of ET-1 mRNA is indeed a target of miR-648.…”

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confidence: 93%

MicroRNA 648 Targets ET-1 mRNA and Is Cotranscriptionally Regulated with MICAL3 by PAX5

Gonsalves

Mpollo

et al. 2015

Molecular and Cellular Biology

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c Pulmonary hypertension (PHT) is associated with high mortality in sickle cell anemia (SCA). Previously, we showed that elevated levels of placenta growth factor (PlGF) in SCA patients correlate with increased levels of the potent vasoconstrictor endothelin-1 (ET-1) and PHT. Moreover, PlGF induced the expression of ET-1 via hypoxia-inducible factor 1␣. Here, we show a novel example of ET-1 posttranscriptional regulation by PlGF via action of microRNA 648 (miR-648), which is subject to transcriptional coregulation with its host gene, MICAL3 (microtubule-associated monooxygenase, calponin, and LIM domain containing 3gene). PlGF repressed expression of miR-648 in endothelial cells. Luciferase reporter assays using wild-type and mutant ET-1 3= untranslated region (UTR) constructs, and transfection of miR-648 mimics showed that miR-648 targets the 3= UTR of ET-1 mRNA. Since miR-648 is located in a 5=-proximal intron of MICAL3, we examined which of three potential promoters was responsible for its expression. The MICAL3 distal promoter (P1) was the predominant promoter used for transcription of premiR-648, and it was under positive control by PAX5 (paired box protein 5) transcription factor, as demonstrated by the loss and gain of function of PAX5 activity, and chromatin immunoprecipitation analysis. These studies provide a novel link wherein PlGF-mediated downregulation of PAX5 attenuates miR-648 expression leading to increased ET-1 levels that are known to induce PHT in SCA. Endothelin-1 (ET-1), a 21-amino-acid peptide hormone primarily synthesized and secreted by endothelium in vivo, is involved in proliferation of smooth muscle cells and vascular tone (1-4). In the vasculature, the endothelin system, comprising endothelin ligands (ET-1, ET-2, and ET-3), endothelin receptors (ET-AR and ET-BR), and two activating peptidases, has a basal vasoconstricting role; dysfunction contributes to the development of diseases such as hypertension and other cardiovascular diseases (3). Hypoxia is a potent inducer of ET-1 gene expression in endothelial cells via activation of hypoxia-inducible factor 1␣ (HIF-1␣) (5, 6).Pulmonary hypertension (PHT), occurs in ca. 10% of adults with sickle cell anemia (SCA), and its diagnosis is associated with a 38 to 40% mortality at 2 to 6 years (7,8). Sickle mice develop PHT with increasing age, manifested as high pulmonary artery pressures and right ventricular hypertrophy (9). Physiological factors implicated in PHT in SCA include endothelial dysfunction, pulmonary vasoconstriction, and vascular remodeling, all of which are associated with chronic hemolysis, hypoxia, hemostatic activation, and inflammation (8, 10-12). ET-1 and nitric oxide (NO) are mutually opposing pulmonary vasoactive factors that regulate pulmonary vascular tone. It is postulated that hemolysis leads to quenching of NO by extracellular/cell-free hemoglobin, thereby reducing NO bioavailability (11, 13), which in turn leads to the clinical manifestations of sickle PHT (13-15). Numerous studies in SCA and other hemolytic anem...

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Rab6, Rab8, and MICAL3 Cooperate in Controlling Docking and Fusion of Exocytotic Carriers

Cited by 177 publications

References 31 publications

Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions

Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

MicroRNA 648 Targets ET-1 mRNA and Is Cotranscriptionally Regulated with MICAL3 by PAX5

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