The centrosome is an actin-organizing centre

Farina, Francesca; Gaillard, Jérémie; Guérin, Christophe; Couté, Yohann; Sillibourne, James; Blanchoin, Laurent; Théry, Manuel

doi:10.1038/ncb3285

Cited by 223 publications

(279 citation statements)

References 68 publications

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“…In cells lacking Macf1, anchoring of microtubules around the basal body was disrupted. PCM1, a protein required for radial organization of microtubules at the basal body (Dammermann and Merdes, 2002; Farina et al, 2016), was also less dispersed in the absence of Macf1. Two other known direct binding partners of Macf1, EB1 and EB3, promote ciliogenesis via microtubule anchoring at the subdistal appendages, similar to the proposed mechanism for Macf1 (Schroder et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Loss of MACF1 Abolishes Ciliogenesis and Disrupts Apicobasal Polarity Establishment in the Retina

et al. 2016

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Summary Microtubule actin crosslinking factor 1 (Macf1) plays a role in the coordination of microtubules and actin in multiple cellular processes. Here we show that Macf1 is also critical for ciliogenesis in multiple cell types. Ablation of Macf1 in the developing retina abolishes ciliogenesis, and basal bodies fail to dock to ciliary vesicles or migrate apically. Photoreceptor polarity is randomized while inner retinal cells laminate correctly, suggesting that photoreceptor maturation is guided by polarity cues provided by cilia. Deletion of Macf1 in adult photoreceptors causes reversal of basal body docking and loss of outer segments, reflecting a continuous requirement for Macf1 function. Macf1 also interacts with the ciliary proteins Mkks and Talpid3. We propose that a disruption of trafficking across microtubles to actin filaments underlies the ciliogenesis defect in cells lacking Macf1, and that Mkks and Talpid3 are involved in the coordination of microtubule and actin interactions.

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Section: Discussionmentioning

confidence: 99%

Loss of MACF1 Abolishes Ciliogenesis and Disrupts Apicobasal Polarity Establishment in the Retina

et al. 2016

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“…The centrosome, consisting of two centrioles and surrounding pericentriolar material (PCM), is a microtubule- and microfilament-organizing center of animal cells (Farina, et al 2016). It regulates cell shape, polarity, migration, and the DNA-damage response and serves as a bustling hub of cellular signaling due to its ability to recruit and concentrate cell cycle, checkpoint, and signaling proteins and other molecules (Conduit, et al 2015; Lerit and Poulton 2015).…”

Section: An Overview Of Centrosome Abnormalitiesmentioning

confidence: 99%

Centrosome amplification: a suspect in breast cancer and racial disparities

Ogden

Rida

Aneja

2017

Endocrine-Related Cancer

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The multifaceted involvement of centrosome amplification (CA) in tumorigenesis is coming into focus following years of meticulous experimentation, which have elucidated the powerful abilities of CA to promote cellular invasion, disrupt stem cell division, drive chromosomal instability (CIN), and perturb tissue architecture, activities that can accelerate tumor progression. Integration of the extant in vitro, in vivo, and clinical data suggests that in some tissues CA may be a tumor-initiating event, in others a consequential “hit” in multistep tumorigenesis, and in still others non-tumorigenic. However, in vivo data are limited, do not specifically include breast models, and primarily focus on PLK4 (which has CA-independent mechanisms by which it promotes aggressive cellular phenotypes). In vitro breast cancer models suggest that CA can promote tumorigenesis in breast cancer cells in the setting of p53 loss or mutation, which can both trigger CA and promote cellular tolerance to its tendency to slow proliferation and induce aneuploidy. It is thus our perspective that CA is likely an early hit in multistep breast tumorigenesis that may sometimes be lost to preserve aggressive karyotypes acquired through centrosome clustering-mediated CIN, both numerical and structural. We also envision that the robust link between p53 and CA may underlie, to a considerable degree, racial health disparity in breast cancer outcomes. This question is clinically significant because, if it is true, then analysis of centrosomal profiles and administration of centrosome declustering drugs could prove highly efficacious in risk stratifying breast cancers and treating African American (AA) women with breast cancer.

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“…Centrosomal F-actin was previously observed (Hubert et al, 2011), but it was not until recently that WASH was identified as the nucleation-promoting factor involved in its generation (Farina et al, 2015). Farina et al found that the accumulation of WASH on centrioles required pericentriolar material protein 1, MTs and dynein.…”

Section: Jmymentioning

confidence: 99%

“…Farina et al found that the accumulation of WASH on centrioles required pericentriolar material protein 1, MTs and dynein. Significantly, depletion of WASH impaired centrosomal F-actin nucleation (Farina et al, 2015). However, the mechanism by which WASH is activated at the centrosome, as well as the contribution of F-actin nucleation to centrosome architecture, positioning and organelle interaction, and the impact of F-actin on primary cilia formation and function remain to be determined.…”

Section: Jmymentioning

confidence: 99%

Cellular functions of WASP family proteins at a glance

Alekhina

Burstein

Billadeau

2017

Journal of Cell Science

165

172

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Proteins of the Wiskott–Aldrich syndrome protein (WASP) family function as nucleation-promoting factors for the ubiquitously expressed Arp2/3 complex, which drives the generation of branched actin filaments. Arp2/3-generated actin regulates diverse cellular processes, including the formation of lamellipodia and filopodia, endocytosis and/or phagocytosis at the plasma membrane, and the generation of cargo-laden vesicles from organelles including the Golgi, endoplasmic reticulum (ER) and the endo-lysosomal network. Recent studies have also identified roles for WASP family members in promoting actin dynamics at the centrosome, influencing nuclear shape and membrane remodeling events leading to the generation of autophagosomes. Interestingly, several WASP family members have also been observed in the nucleus where they directly influence gene expression by serving as molecular platforms for the assembly of epigenetic and transcriptional machinery. In this Cell Science at a Glance article and accompanying poster, we provide an update on the subcellular roles of WHAMM, JMY and WASH (also known as WASHC1), as well as their mechanisms of regulation and emerging functions within the cell.

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The centrosome is an actin-organizing centre

Cited by 223 publications

References 68 publications

Loss of MACF1 Abolishes Ciliogenesis and Disrupts Apicobasal Polarity Establishment in the Retina

Loss of MACF1 Abolishes Ciliogenesis and Disrupts Apicobasal Polarity Establishment in the Retina

Centrosome amplification: a suspect in breast cancer and racial disparities

Cellular functions of WASP family proteins at a glance

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