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 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 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.

scholarly journals Cytoplasmic transport and nuclear import of plasmid DNA

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Haiqing Bai ◽  
Gillian M. Schiralli Lester ◽  
Laura C. Petishnok ◽  
David A. Dean
Keyword(s):  
Nuclear Envelope ◽  
Model Systems ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Microtubule Organizing Center ◽  
Microtubule Network ◽  
Naked Dna ◽  
Cytoplasmic Transport ◽  
Organizing Center ◽  
Pore Complexes

Productive transfection and gene transfer require not simply the entry of DNA into cells and subsequent transcription from an appropriate promoter, but also a number of intracellular events that allow the DNA to move from the extracellular surface of the cell into and through the cytoplasm, and ultimately across the nuclear envelope and into the nucleus before any transcription can initiate. Immediately upon entry into the cytoplasm, naked DNA, either delivered through physical techniques or after disassembly of DNA–carrier complexes, associates with a large number of cellular proteins that mediate subsequent interactions with the microtubule network for movement toward the microtubule organizing center and the nuclear envelope. Plasmids then enter the nucleus either upon the mitotic disassembly of the nuclear envelope or through nuclear pore complexes in the absence of cell division, using a different set of proteins. This review will discuss our current understanding of these pathways used by naked DNA during the transfection process. While much has been elucidated on these processes, much remains to be discerned, but with the development of a number of model systems and approaches, great progress is being made.

scholarly journals Cytoskeletal Interactions at the Nuclear Envelope Mediated by Nesprins

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Surayya Taranum ◽  
Ilknur Sur ◽  
Rolf Müller ◽  
Wenshu Lu ◽  
R. N. Rashmi ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Envelope Protein ◽  
Transmembrane Domain ◽  
Ectopic Expression ◽  
Actin Binding ◽  
Actin Binding Domain ◽  
Cytoskeletal Networks ◽  
Filament Network ◽  
Spectrin Repeats

Nesprin-1 is a giant tail-anchored nuclear envelope protein composed of an N-terminal F-actin binding domain, a long linker region formed by multiple spectrin repeats and a C-terminal transmembrane domain. Based on this structure, it connects the nucleus to the actin cytoskeleton. Earlier reports had shown that Nesprin-1 binds to nuclear envelope proteins emerin and lamin through C-terminal spectrin repeats. These repeats can also self-associate. We focus on the N-terminal Nesprin-1 sequences and show that they interact with Nesprin-3, a further member of the Nesprin family, which connects the nucleus to the intermediate filament network. We show that upon ectopic expression of Nesprin-3 in COS7 cells, which are nearly devoid of Nesprin-3 in vitro, vimentin filaments are recruited to the nucleus and provide evidence for an F-actin interaction of Nesprin-3 in vitro. We propose that Nesprins through interactions amongst themselves and amongst the various Nesprins form a network around the nucleus and connect the nucleus to several cytoskeletal networks of the cell.

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

2020 ◽  
Author(s):  
Silvia Vergarajauregui ◽  
Robert Becker ◽  
Ulrike Steffen ◽  
Maria Sharkova ◽  
Tilman Esser ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Author Response ◽  
Microtubule Organizing Center ◽  
Organizing Center

scholarly journals Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
David C Zebrowski ◽  
Silvia Vergarajauregui ◽  
Chi-Chung Wu ◽  
Tanja Piatkowski ◽  
Robert Becker ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nuclear Envelope ◽  
Regenerative Therapy ◽  
Microtubule Organizing Center ◽  
Potential Explanation ◽  
Cycle Arrest ◽  
Adult Cardiomyocytes ◽  
Organizing Center ◽  
G1 Cell Cycle Arrest ◽  
Center Loss

Mammalian cardiomyocytes become post-mitotic shortly after birth. Understanding how this occurs is highly relevant to cardiac regenerative therapy. Yet, how cardiomyocytes achieve and maintain a post-mitotic state is unknown. Here, we show that cardiomyocyte centrosome integrity is lost shortly after birth. This is coupled with relocalization of various centrosome proteins to the nuclear envelope. Consequently, postnatal cardiomyocytes are unable to undergo ciliogenesis and the nuclear envelope adopts the function as cellular microtubule organizing center. Loss of centrosome integrity is associated with, and can promote, cardiomyocyte G0/G1 cell cycle arrest suggesting that centrosome disassembly is developmentally utilized to achieve the post-mitotic state in mammalian cardiomyocytes. Adult cardiomyocytes of zebrafish and newt, which are able to proliferate, maintain centrosome integrity. Collectively, our data provide a novel mechanism underlying the post-mitotic state of mammalian cardiomyocytes as well as a potential explanation for why zebrafish and newts, but not mammals, can regenerate their heart.

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.

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