scholarly journals Myogenin controls via AKAP6 non-centrosomal microtubule organizing center formation at the nuclear envelope

2020 ◽  
Author(s):  
Robert Becker ◽  
Silvia Vergarajauregui ◽  
Florian Billing ◽  
Maria Sharkova ◽  
Eleonora Lippolis ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Nuclear Envelope ◽  
Muscle Cells ◽  
Cell Types ◽  
Microtubule Organizing Center ◽  
Anchor Protein ◽  
Organizing Center ◽  
Multiple Cell ◽  
Promoter Studies ◽  
Centrosomal Proteins

AbstractNon-centrosomal microtubule organizing centers (ncMTOC) are pivotal for the function of multiple cell types, but the processes initiating their formation are unknown. Here, we find that the transcription factor myogenin is required in myoblasts for recruiting centrosomal proteins. Moreover, myogenin is sufficient in fibroblasts for ncMTOC formation and centrosome attenuation. Bioinformatics combined with loss- and gain-of-function experiments identified induction of AKAP6 expression as one central mechanism for myogenin-mediated ncMTOC formation. Promoter studies indicate that myogenin preferentially induces the transcription of muscle- and ncMTOC-specific isoforms of Akap6 and Syne1, which encodes nesprin-1α, the ncMTOC anchor protein in muscle cells. Overexpression of AKAP6β and nesprin-1α was sufficient to recruit endogenous centrosomal proteins to the nuclear envelope of myoblasts in the absence of myogenin. Taken together, our results illuminate how mammals transcriptionally control the switch from a centrosomal MTOC to an ncMTOC and identify AKAP6 as a novel ncMTOC component in muscle cells.

scholarly journals Myogenin controls via AKAP6 non-centrosomal microtubule organizing center formation at the nuclear envelope

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Robert Becker ◽  
Silvia Vergarajauregui ◽  
Florian Billing ◽  
Maria Sharkova ◽  
Eleonora Lippolis ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Nuclear Envelope ◽  
Muscle Cells ◽  
Cell Types ◽  
Microtubule Organizing Center ◽  
Gain Of Function ◽  
Anchor Protein ◽  
Organizing Center ◽  
Multiple Cell ◽  
Promoter Studies

Non-centrosomal microtubule organizing centers (MTOC) are pivotal for the function of multiple cell types, but the processes initiating their formation are unknown. Here, we find that the transcription factor myogenin is required in murine myoblasts for the localization of MTOC proteins to the nuclear envelope. Moreover, myogenin is sufficient in fibroblasts for nuclear envelope MTOC (NE-MTOC) formation and centrosome attenuation. Bioinformatics combined with loss- and gain-of-function experiments identified induction of AKAP6 expression as one central mechanism for myogenin-mediated NE-MTOC formation. Promoter studies indicate that myogenin preferentially induces the transcription of muscle- and NE-MTOC-specific isoforms of Akap6 and Syne1, which encodes nesprin-1α, the NE-MTOC anchor protein in muscle cells. Overexpression of AKAP6β and nesprin-1α was sufficient to recruit endogenous MTOC proteins to the nuclear envelope of myoblasts in the absence of myogenin. Taken together, our results illuminate how mammals transcriptionally control the switch from a centrosomal MTOC to an NE-MTOC and identify AKAP6 as a novel NE-MTOC component in muscle cells.

scholarly journals Microtubule Organization in Striated Muscle Cells

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1395 ◽  
Author(s):  
Robert Becker ◽  
Marina Leone ◽  
Felix Engel
Keyword(s):  
Nuclear Envelope ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Striated Muscle ◽  
Muscle Cells ◽  
Cell Types ◽  
Microtubule Organizing Center ◽  
Microtubule Organization ◽  
Cardiac Muscle Cells ◽  
Microtubule Networks

Distinctly organized microtubule networks contribute to the function of differentiated cell types such as neurons, epithelial cells, skeletal myotubes, and cardiomyocytes. In striated (i.e., skeletal and cardiac) muscle cells, the nuclear envelope acts as the dominant microtubule-organizing center (MTOC) and the function of the centrosome—the canonical MTOC of mammalian cells—is attenuated, a common feature of differentiated cell types. We summarize the mechanisms known to underlie MTOC formation at the nuclear envelope, discuss the significance of the nuclear envelope MTOC for muscle function and cell cycle progression, and outline potential mechanisms of centrosome attenuation.

scholarly journals AKAP6 orchestrates the nuclear envelope microtubule-organizing center by linking golgi and nucleus via AKAP9

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Silvia Vergarajauregui ◽  
Robert Becker ◽  
Ulrike Steffen ◽  
Maria Sharkova ◽  
Tilman Esser ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Nuclear Envelope ◽  
Ectopic Expression ◽  
Cardiomyocyte Hypertrophy ◽  
Microtubule Organizing Center ◽  
Rat Cardiomyocytes ◽  
Organizing Center ◽  
Centrosomal Proteins ◽  
Human Osteoclasts ◽  
Spectrin Repeats

The switch from centrosomal microtubule-organizing centers (MTOCs) to non-centrosomal MTOCs during differentiation is poorly understood. Here, we identify AKAP6 as key component of the nuclear envelope MTOC. In rat cardiomyocytes, AKAP6 anchors centrosomal proteins to the nuclear envelope through its spectrin repeats, acting as an adaptor between nesprin-1α and Pcnt or AKAP9. In addition, AKAP6 and AKAP9 form a protein platform tethering the Golgi to the nucleus. Both Golgi and nuclear envelope exhibit MTOC activity utilizing either AKAP9, or Pcnt-AKAP9, respectively. AKAP6 is also required for formation and activity of the nuclear envelope MTOC in human osteoclasts. Moreover, ectopic expression of AKAP6 in epithelial cells is sufficient to recruit endogenous centrosomal proteins. Finally, AKAP6 is required for cardiomyocyte hypertrophy and osteoclast bone resorption activity. Collectively, we decipher the MTOC at the nuclear envelope as a bi-layered structure generating two pools of microtubules with AKAP6 as a key organizer.

scholarly journals HOT or not: examining the basis of high-occupancy target regions

2017 ◽  
Author(s):  
Katarzyna Wreczycka ◽  
Vedran Franke ◽  
Bora Uyar ◽  
Ricardo Wurmus ◽  
Altuna Akalin
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Cell Types ◽  
Data Sets ◽  
Gene Promoters ◽  
Quadruplex Dna ◽  
Golden Standard ◽  
Multiple Cell ◽  
Multiple Species

AbstractHigh-occupancy target (HOT) regions are the segments of the genome with unusually high number of transcription factor binding sites. These regions are observed in multiple species and thought to have biological importance due to high transcription factor occupancy. Furthermore, they coincide with house-keeping gene promoters and the associated genes are stably expressed across multiple cell types. Despite these features, HOT regions are solemnly defined using ChIP-seq experiments and shown to lack canonical motifs for transcription factors that are thought to be bound there. Although, ChIP-seq experiments are the golden standard for finding genome-wide binding sites of a protein, they are not noise free. Here, we show that HOT regions are likely to be ChIP-seq artifacts and they are similar to previously proposed “hyper-ChIPable” regions. Using ChIP-seq data sets for knocked-out transcription factors, we demonstrate presence of false positive signals on HOT regions. We observe sequence characteristics and genomic features that are discriminatory of HOT regions, such as GC/CpG-rich k-mers and enrichment of RNA-DNA hybrids (R-loops) and DNA tertiary structures (G-quadruplex DNA). The artificial ChIP-seq enrichment on HOT regions could be associated to these discriminatory features. Furthermore, we propose strategies to deal with such artifacts for the future ChIP-seq studies.

scholarly journals The role of Aspergillus nidulans polo-like kinase PlkA in microtubule-organizing center control

2021 ◽  
Author(s):  
Xiaolei Gao ◽  
Saturnino Herrero ◽  
Valentin Wernet ◽  
Sylvia Erhardt ◽  
Oliver Valerius ◽  
...  
Keyword(s):  
Aspergillus Nidulans ◽  
Cell Types ◽  
Spindle Pole ◽  
Receptor Protein ◽  
Animal Cells ◽  
Microtubule Organizing Center ◽  
Spindle Pole Bodies ◽  
Organizing Center ◽  
Ring Complex ◽  
Core Components

Centrosomes are important microtubule-organizing centers (MTOC) in animal cells. In addition, non-centrosomal MTOCs (ncMTOCs) were described in many cell types. Functional analogs of centrosomes in fungi are the spindle pole bodies (SPBs). In Aspergillus nidulans additional MTOCs were discovered at septa (sMTOC). Although the core components are conserved in both MTOCs, their composition and organization are different and dynamic. Here, we show that the polo-like kinase PlkA binds the γ-tubulin ring complex (γ-TuRC) receptor protein ApsB and contributes to targeting ApsB to both MTOCs. PlkA coordinates SPB outer plaque with sMTOC activities. PlkA kinase activity was required for astral MT formation involving ApsB recruitment. PlkA also interacted with the γ-TuRC inner plaque receptor protein PcpA. Mitosis was delayed without PlkA, and the PlkA protein was required for proper mitotic spindle morphology, although this function was independent of its catalytic activity. Our results suggest polo-like kinase as a regulator of MTOC activities and as a scaffolding unit through interaction with γ-tubulin ring complex receptors.

scholarly journals Centrosomal and Non-Centrosomal Microtubule-Organizing Centers (MTOCs) in Drosophila melanogaster

Cells ◽  
2018 ◽  
Vol 7 (9) ◽  
pp. 121 ◽  
Author(s):  
Marisa Tillery ◽  
Caitlyn Blake-Hedges ◽  
Yiming Zheng ◽  
Rebecca Buchwalter ◽  
Timothy Megraw
Keyword(s):  
Current Knowledge ◽  
Cell Types ◽  
Wing Disc ◽  
Early Embryo ◽  
Microtubule Organizing Center ◽  
Drosophila Development ◽  
Functional Roles ◽  
Animal Development ◽  
Microtubule Organizing Centers ◽  
Organizing Center

The centrosome is the best-understood microtubule-organizing center (MTOC) and is essential in particular cell types and at specific stages during Drosophila development. The centrosome is not required zygotically for mitosis or to achieve full animal development. Nevertheless, centrosomes are essential maternally during cleavage cycles in the early embryo, for male meiotic divisions, for efficient division of epithelial cells in the imaginal wing disc, and for cilium/flagellum assembly in sensory neurons and spermatozoa. Importantly, asymmetric and polarized division of stem cells is regulated by centrosomes and by the asymmetric regulation of their microtubule (MT) assembly activity. More recently, the components and functions of a variety of non-centrosomal microtubule-organizing centers (ncMTOCs) have begun to be elucidated. Throughout Drosophila development, a wide variety of unique ncMTOCs form in epithelial and non-epithelial cell types at an assortment of subcellular locations. Some of these cell types also utilize the centrosomal MTOC, while others rely exclusively on ncMTOCs. The impressive variety of ncMTOCs being discovered provides novel insight into the diverse functions of MTOCs in cells and tissues. This review highlights our current knowledge of the composition, assembly, and functional roles of centrosomal and non-centrosomal MTOCs in Drosophila.

Spectrin alpha is important for rear polarization of the microtubule organizing center during migration and spindle pole assembly during division of neointimal smooth muscle cells

Cytoskeleton ◽  
2015 ◽  
Vol 72 (4) ◽  
pp. 157-170 ◽  
Author(s):  
Rosalind V. Silverman-Gavrila ◽  
Lorelei B. Silverman-Gavrila ◽  
Khawaja Hasan Bilal ◽  
Michelle P. Bendeck
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Spindle Pole ◽  
Microtubule Organizing Center ◽  
Organizing Center

scholarly journals Rear Polarization of the Microtubule-Organizing Center in Neointimal Smooth Muscle Cells Depends on PKCα, ARPC5, and RHAMM

2011 ◽  
Vol 178 (2) ◽  
pp. 895-910 ◽  
Author(s):  
Rosalind Silverman-Gavrila ◽  
Lorelei Silverman-Gavrila ◽  
Guangpei Hou ◽  
Ming Zhang ◽  
Milton Charlton ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Microtubule Organizing Center ◽  
Organizing Center

scholarly journals Brr6 drives the Schizosaccharomyces pombe spindle pole body nuclear envelope insertion/extrusion cycle

2011 ◽  
Vol 195 (3) ◽  
pp. 467-484 ◽  
Author(s):  
Tiina Tamm ◽  
Agnes Grallert ◽  
Emily P.S. Grossman ◽  
Isabel Alvarez-Tabares ◽  
Frances E. Stevens ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
Mitotic Exit ◽  
Microtubule Organizing Center ◽  
Pole Body ◽  
Cytoplasmic Face ◽  
Organizing Center ◽  
Nuclear Component ◽  
Anaphase B

The fission yeast interphase spindle pole body (SPB) is a bipartite structure in which a bulky cytoplasmic domain is separated from a nuclear component by the nuclear envelope. During mitosis, the SPB is incorporated into a fenestra that forms within the envelope during mitotic commitment. Closure of this fenestra during anaphase B/mitotic exit returns the cytoplasmic component to the cytoplasmic face of an intact interphase nuclear envelope. Here we show that Brr6 is transiently recruited to SPBs at both SPB insertion and extrusion. Brr6 is required for both SPB insertion and nuclear envelope integrity during anaphase B/mitotic exit. Genetic interactions with apq12 and defective sterol assimilation suggest that Brr6 may alter envelope composition at SPBs to promote SPB insertion and extrusion. The restriction of the Brr6 domain to eukaryotes that use a polar fenestra in an otherwise closed mitosis suggests a conserved role in fenestration to enable a single microtubule organizing center to nucleate both cytoplasmic and nuclear microtubules on opposing sides of the nuclear envelope.

Mechanisms regulating the vascular smooth muscle Na/H exchanger (NHE-1) in diabetes

1998 ◽  
Vol 76 (5) ◽  
pp. 751-759 ◽  
Author(s):  
Katherine M Hannan ◽  
Peter J Little
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Hydrogen Exchange ◽  
Muscle Cells ◽  
Cell Types ◽  
Sodium Hydrogen ◽  
Sodium Hydrogen Exchanger ◽  
Multiple Cell

Vascular disease is a major component of the complications associated with diabetes. The pathology involves hypertrophy and proliferation of vascular smooth muscle cells and the production and modification of extracellular matrix. The sodium/hydrogen exchanger has been widely implicated in the growth of multiple cell types, including vascular smooth muscle. Increases in sodium/hydrogen exchange activity serve as an effector or at least as an indicator of vascular activation. This article is concerned with the role of the biochemical abnormalities of diabetes exerting their pathological effects on vascular smooth muscle cells via altering sodium/hydrogen exchange activity.Key words: diabetes, sodium/hydrogen exchanger, vascular smooth muscle, complications.

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