scholarly journals Alpha 6 integrins promote cytokinesis by regulating the expression of RSK2 and MKLP1

2019 ◽  
Author(s):  
Neetu Singh ◽  
Hao Xu ◽  
Renee Thiemann ◽  
Kara A. DeSantis ◽  
Melinda Larsen ◽  
...  
Keyword(s):  
Cell Division ◽  
Normal Development ◽  
Intercellular Bridge ◽  
S6 Kinase ◽  
Cellular Processes ◽  
Daughter Cells ◽  
Cytoplasmic Material ◽  
Ribosomal S6 Kinase 2 ◽  
Ribosomal S6 Kinase ◽  
Salivary Gland Epithelial Cells

ABSTRACTThe integrin-mediated interaction of cells with components of the extracellular matrix (ECM) regulates many cellular processes including cell division. Cytokinesis is the last step of cell division and is critical for normal development and tissue homeostasis as it ensures the proper segregation of genetic and cytoplasmic material between daughter cells. Cytokinesis failure leads to defects in development and tissue differentiation, as well as tumorigenesis. Abscission of intercellular bridge that connects presumptive daughter cells is the last step of cell division. The mitotic kinesin-like protein 1 (MKLP1) plays a central role in positioning the abscission machinery. Here, we show that α6 integrins promote successful cytokinesis in salivary gland epithelial cells by regulating the expression of MKLP1. RNAi-mediated depletion of α6 integrins inhibits cytokinesis and the expression of MKLP1 and p90 ribosomal-S6-kinase 2 (RSK2). Depletion of RSK2 results in similar defects in cytokinesis and also inhibits the expression of MKLP1, suggesting that the expression of RSK2 is required downstream of integrins to promote MKLP1 expression and successful cytokinesis. RNAi-mediated depletion of RSK2 in embryonic salivary glands in organ culture also results in the inhibition of cytokinesis and MKLP1 expression, indicating the physiological significance of this pathway.

scholarly journals Midbody: From the Regulator of Cytokinesis to Postmitotic Signaling Organelle

Medicina ◽  
2018 ◽  
Vol 54 (4) ◽  
pp. 53 ◽  
Author(s):  
Ieva Antanavičiūtė ◽  
Paulius Gibieža ◽  
Rytis Prekeris ◽  
Vytenis Skeberdis
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Intercellular Bridge ◽  
Large Protein ◽  
Daughter Cells ◽  
First Case ◽  
Tumorigenic Potential ◽  
The One ◽  
And Function ◽  
Protein Rich

Faithful cell division is crucial for successful proliferation, differentiation, and development of cells, tissue homeostasis, and preservation of genomic integrity. Cytokinesis is a terminal stage of cell division, leaving two genetically identical daughter cells connected by an intercellular bridge (ICB) containing the midbody (MB), a large protein-rich organelle, in the middle. Cell division may result in asymmetric or symmetric abscission of the ICB. In the first case, the ICB is severed on the one side of the MB, and the MB is inherited by the opposite daughter cell. In the second case, the MB is cut from both sides, expelled into the extracellular space, and later it can be engulfed by surrounding cells. Cells with lower autophagic activity, such as stem cells and cancer stem cells, are inclined to accumulate MBs. Inherited MBs affect cell polarity, modulate intra- and intercellular communication, enhance pluripotency of stem cells, and increase tumorigenic potential of cancer cells. In this review, we briefly summarize the latest knowledge on MB formation, inheritance, degradation, and function, and in addition, present and discuss our recent findings on the electrical and chemical communication of cells connected through the MB-containing ICB.

scholarly journals Exogenously Added Fibroblast Growth Factor 2 (FGF-2) to NIH3T3 CellsInteracts with Nuclear Ribosomal S6 Kinase 2 (RSK2) in a Cell Cycle-dependentManner*

2005 ◽  
Vol 280 (27) ◽  
pp. 25604-25610 ◽  
Author(s):  
Fabienne Soulet ◽  
Karine Bailly ◽  
Stéphane Roga ◽  
Anne-Claire Lavigne ◽  
François Amalric ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
S6 Kinase ◽  
Ribosomal S6 Kinase 2 ◽  
A Cell ◽  
Ribosomal S6 Kinase

P90 Ribosomal s6 kinase 2 negatively regulates axon growth in motoneurons

2009 ◽  
Vol 42 (2) ◽  
pp. 134-141 ◽  
Author(s):  
Matthias Fischer ◽  
Patricia Marques Pereira ◽  
Bettina Holtmann ◽  
Christian M. Simon ◽  
Andre Hanauer ◽  
...  
Keyword(s):  
Axon Growth ◽  
S6 Kinase ◽  
Ribosomal S6 Kinase 2 ◽  
P90 Ribosomal S6 Kinase ◽  
Ribosomal S6 Kinase

scholarly journals The p53 Protein Is a Novel Substrate of Ribosomal S6 Kinase 2 and a Critical Intermediary for Ribosomal S6 Kinase 2 and Histone H3 Interaction

2005 ◽  
Vol 65 (9) ◽  
pp. 3596-3603 ◽  
Author(s):  
Yong-Yeon Cho ◽  
Zhiwei He ◽  
Yiguo Zhang ◽  
Hong Seok Choi ◽  
Feng Zhu ◽  
...  
Keyword(s):  
P53 Protein ◽  
Histone H3 ◽  
S6 Kinase ◽  
Ribosomal S6 Kinase 2 ◽  
Ribosomal S6 Kinase

scholarly journals Ribosomal S6 Kinase (RSK) Regulates Phosphorylation of Filamin A on an Important Regulatory Site

2004 ◽  
Vol 24 (7) ◽  
pp. 3025-3035 ◽  
Author(s):  
Michele S. Woo ◽  
Yasutaka Ohta ◽  
Isaac Rabinovitz ◽  
Thomas P. Stossel ◽  
John Blenis
Keyword(s):  
Map Kinase ◽  
Kinase Domain ◽  
Filamin A ◽  
S6 Kinase ◽  
Membrane Ruffling ◽  
Cellular Processes ◽  
Mitogen Activated Protein ◽  
Epidermal Growth ◽  
Ribosomal S6 Kinase

ABSTRACT The Ras-mitogen-activated protein (Ras-MAP) kinase pathway regulates various cellular processes, including gene expression, cell proliferation, and survival. Ribosomal S6 kinase (RSK), a key player in this pathway, modulates the activities of several cytoplasmic and nuclear proteins via phosphorylation. Here we report the characterization of the cytoskeletal protein filamin A (FLNa) as a membrane-associated RSK target. We show that the N-terminal kinase domain of RSK phosphorylates FLNa on Ser2152 in response to mitogens. Inhibition of MAP kinase signaling with UO126 or mutation of Ser2152 to Ala on FLNa prevents epidermal growth factor (EGF)-stimulated phosphorylation of FLNa in vivo. Furthermore, phosphorylation of FLNa on Ser2152 is significantly enhanced by the expression of wild-type RSK and antagonized by kinase-inactive RSK or specific reduction of endogenous RSK. Strikingly, EGF-induced, FLNa-dependent migration of human melanoma cells is significantly reduced by UO126 treatment. Together, these data provide substantial evidence that RSK phosphorylates FLNa on Ser2152 in vivo. Given that phosphorylation of FLNa on Ser2152 is required for Pak1-mediated membrane ruffling, our results suggest a novel role for RSK in the regulation of the actin cytoskeleton.

scholarly journals Cell-type selective deletion of RSK2 reveals insights into altered signaling in Coffin-Lowry Syndrome

2017 ◽  
Author(s):  
Hu Zhu ◽  
Ryan T. Strachan ◽  
Daniel Urban ◽  
Martilias Farrell ◽  
Wesley K. Kroeze ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Pyramidal Neurons ◽  
Receptor Protein ◽  
Receptor Signaling ◽  
Loss Of Function ◽  
Intracellular Loop ◽  
S6 Kinase ◽  
Ribosomal S6 Kinase 2 ◽  
Ribosomal S6 Kinase

Coffin-Lowry syndrome (CLS) is an X-linked syndromic form of mental retardation characterized by various skeletal dysmorphisms, moderate to severe mental retardation, and in some cases, psychosis. CLS is caused by loss-of-function mutations of the p90 ribosomal S6 kinase 2 (RPS6KA3) gene encoding a growth factor-regulated serine/threonine kinase, ribosomal S6 kinase 2 (RSK2). We previously identified RSK2 as a novel interacting protein that tonically inhibits 5-HT2A receptor signaling by phosphorylating Ser-314 within the third intracellular loop. To determine if RSK2 inhibits 5-HT2A receptor signaling in vivo and whether disruption of RSK2 could lead to schizophrenia-like behaviors - as is seen in some CLS patients - we genetically disrupted the function of RSK2 either globally or selectively in forebrain pyramidal neurons in mice. Both global and forebrain-selective RSK2 deletion augmented the locomotor responses to the psychotomimetic drugs phencyclidine (PCP) and amphetamine (AMPH). Significantly, forebrain-selective deletion of RSK2 augmented 5-HT2A receptor signaling as exemplified by enhanced 5-HT2A-mediated c-fos activation and head-twitch response without altering the levels or distribution of 5-HT2A receptor protein. Thus, RSK2 modulates 5HT2A receptor function in vivo, and disruption of RSK2 leads to augmented psychostimulant-induced responses reminiscent of those seen in many animal models of schizophrenia. These findings strengthen the association between 5-HT2A receptor dysfunction and psychosis, and provide a potential mechanism underlying the schizophrenia-like symptoms present in some CLS patients.

scholarly journals Extrachromosomal Histone H2B Contributes to the Formation of the Abscission Site for Cell Division

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1391 ◽  
Author(s):  
Laura Monteonofrio ◽  
Davide Valente ◽  
Cinzia Rinaldo ◽  
Silvia Soddu
Keyword(s):  
Cell Division ◽  
Chromatin Structure ◽  
Late Stage ◽  
Intercellular Bridge ◽  
Histone H2b ◽  
Physical Separation ◽  
Daughter Cells ◽  
Dna And Rna ◽  
Constitutive Components

Histones are constitutive components of nucleosomes and key regulators of chromatin structure. We previously observed that an extrachromosomal histone H2B (ecH2B) localizes at the intercellular bridge (ICB) connecting the two daughter cells during cytokinesis independently of DNA and RNA. Here, we show that ecH2B binds and colocalizes with CHMP4B, a key component of the ESCRT-III machinery responsible for abscission, the final step of cell division. Abscission requires the formation of an abscission site at the ICB where the ESCRT-III complex organizes into narrowing cortical helices that drive the physical separation of sibling cells. ecH2B depletion does not prevent membrane cleavage rather results in abscission delay and accumulation of abnormally long and thin ICBs. In the absence of ecH2B, CHMP4B and other components of the fission machinery, such as IST1 and Spastin, are recruited to the ICB and localize at the midbody. However, in the late stage of abscission, these fission factors fail to re-localize at the periphery of the midbody and the abscission site fails to form. These results show that extrachromosomal activity of histone H2B is required in the formation of the abscission site and the proper localization of the fission machinery.

Sign in / Sign up

Export Citation Format

Share Document