16 research outputs found
The mitosis-to-interphase transition is coordinated by cross talk between the SIN and MOR pathways in Schizosaccharomyces pombe
No full textThe mechanisms that regulate cytoskeletal remodeling during the transition between mitosis and interphase are poorly understood. In fission yeast the MOR pathway promotes actin polarization to cell tips in interphase, whereas the SIN signaling pathway drives actomyosin ring assembly and cytokinesis. We show that the SIN inhibits MOR signaling in mitosis by interfering with Nak1 kinase-mediated activation of the most downstream MOR component, the NDR family kinase Orb6. Inactivation of the MOR may be a key function of the SIN because attenuation of MOR signaling rescued the cytokinetic defects of SIN mutants and allowed weak SIN signaling to trigger ectopic cytokinesis. Furthermore, failure to inhibit the MOR is toxic when the cell division apparatus is compromised. Together, our results reveal a mutually antagonistic relationship between the SIN and MOR pathways, which is important for completion of cytokinesis and coordination of cytoskeletal remodeling at the mitosis-to-interphase transition
Elucidation of the Multi-Faceted Roles of the SIN (Septation Initiation Network); Understanding How the SIN Promotes Cytokinesis and Inhibits Interphase Growth in the Fission Yeast Schizosaccharomyces pombe: A Dissertation
No full textCytokinesis is the cytoplasmic division of one cell into two independent daughter cells. Precise regulation of cytokinesis during cell cycle is essential for healthy and rapid multiplication of any organism. Schizosaccharomyces pombe has emerged as an excellent model system to study eukaryotic cell division regulation. This rod shaped organism grows by bipolar elongation in interphase when its actin cytoskeleton is concentrated at the cell ends (poles). However, growth stops in mitosis and the actin cytoskeleton is rearranged to facilitate assembly of the contractile actomyosin ring at the cell middle. Although several studies have focused on the separate processes of growth and division, it was unclear how cells regulate the cytoskeletal remodeling during the transition between the different stages of the cell cycle. The Septation Initiation Network (SIN) is a signaling cascade essential for fission yeast cytokinesis (Balasubramanian et al., 1998; Mishra et al., 2004) and the MOR (morphogenesis) signaling pathway is essential for interphase bipolar growth (Kanai et al, 2005). Interestingly, inactivation of the SIN not only failed to maintain the cytokinetic apparatus at the cell middle but also caused the redistribution of the cytoskeletal elements like actin to the cell ends that led to bipolar cell elongation similar to cells in interphase (Mishra et al., 2004). These results suggested that SIN signaling inhibits interphase bipolar growth, but it was not clear if the SIN had a direct role in inhibition of interphase growth during mitosis and this question was the major focus of this thesis. The results presented in Chapter II show a novel cross-pathway interaction between the SIN and the MOR in the fission yeast. Our results in Chapter III suggest that some of the MOR pathway components might be important for coordination between nuclear and cytoplasmic divisions in mitosis, revealing novel roles of the pathway. In a separate study (Chapter IV) we sought to identify additional regulators of the SIN and cytokinesis through a suppressor screen and found that the nucleolar rDNA transcription machinery inhibits cytokinesis in fission yeast.Interdisciplinary Graduate Progra
Regulation of asymmetric cell division in the epidermis
No full textAbstract For proper tissue morphogenesis, cell divisions and cell fate decisions must be tightly and coordinately regulated. One elegant way to accomplish this is to couple them with asymmetric cell divisions. Progenitor cells in the developing epidermis undergo both symmetric and asymmetric cell divisions to balance surface area growth with the generation of differentiated cell layers. Here we review the molecular machinery implicated in controlling asymmetric cell division. In addition, we discuss the ability of epidermal progenitors to choose between symmetric and asymmetric divisions and the key regulatory points that control this decision.</p
Colloidal Molybdenum Diselenide Nanocrystals for Tunable Broadband, and Mixed-Dimensional Photodetectors
No full textMinimax estimation of low-rank quantum states and their linear functionals
No full textIn classical statistics, a well known paradigm consists in establishing
asymptotic equivalence between an experiment of i.i.d. observations and a
Gaussian shift experiment, with the aim of obtaining optimal estimators in the
former complicated model from the latter simpler model. In particular, a
statistical experiment consisting of i.i.d observations from d-dimensional
multinomial distributions can be well approximated by an experiment consisting
of dimensional Gaussian distributions. In a quantum version of the
result, it has been shown that a collection of qudits (d-dimensional
quantum states) of full rank can be well approximated by a quantum system
containing a classical part, which is a dimensional Gaussian
distribution, and a quantum part containing an ensemble of shifted
thermal states. In this paper, we obtain a generalization of this result when
the qudits are not of full rank. We show that when the rank of the qudits is
, then the limiting experiment consists of an dimensional Gaussian
distribution and an ensemble of both shifted pure and shifted thermal states.
For estimation purposes, we establish an asymptotic minimax result in the
limiting Gaussian model. Analogous results are then obtained for estimation of
a low-rank qudit from an ensemble of identically prepared, independent quantum
systems, using the local asymptotic equivalence result. We also consider the
problem of estimation of a linear functional of the quantum state. We construct
an estimator for the functional, analyze the risk and use quantum local
asymptotic equivalence to show that our estimator is also optimal in the
minimax sense.Comment: arXiv admin note: text overlap with arXiv:0804.3876 by other author
Identification of SIN pathway targets reveals mechanisms of crosstalk between NDR kinase pathways
No full textFirst author Sneha Gupta is a doctoral student in the Interdisciplinary Graduate Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.The septum initiation network (SIN) regulates multiple functions during late mitosis to ensure successful completion of cytokinesis in Schizosaccharomyces pombe. One mechanism by which the SIN promotes cytokinesis is by inhibiting a competing polarity pathway called the MOR, which is required for initiation of polarized growth following completion of cytokinesis. Mutual antagonism between the two NDR kinase pathways, SIN and MOR, is required to coordinate cytoskeletal rearrangements during the mitosis-interphase transition. To determine how the SIN regulates the MOR pathway, we developed a proteomics approach that allowed us to identify multiple substrates of the SIN effector kinase Sid2, including the MOR pathway components Nak1 kinase and an associated protein, Sog2. We show that Sid2 phosphorylation of Nak1 causes removal of Nak1 from the spindle pole bodies, which may both relieve Nak1 inhibition of the SIN and block MOR signaling by preventing interaction of Nak1 with the scaffold protein Mor2. Because the SIN and MOR are conserved in mammalian cells (Hippo and Ndr1/2 pathways, respectively), this work may provide important insight into how the activities of these essential pathways are coordinated
The mitosis-to-interphase transition is coordinated by cross talk between the SIN and MOR pathways in Schizosaccharomyces pombe
No full textThe mechanisms that regulate cytoskeletal remodeling during the transition between mitosis and interphase are poorly understood. In fission yeast the MOR pathway promotes actin polarization to cell tips in interphase, whereas the SIN signaling pathway drives actomyosin ring assembly and cytokinesis. We show that the SIN inhibits MOR signaling in mitosis by interfering with Nak1 kinase-mediated activation of the most downstream MOR component, the NDR family kinase Orb6. Inactivation of the MOR may be a key function of the SIN because attenuation of MOR signaling rescued the cytokinetic defects of SIN mutants and allowed weak SIN signaling to trigger ectopic cytokinesis. Furthermore, failure to inhibit the MOR is toxic when the cell division apparatus is compromised. Together, our results reveal a mutually antagonistic relationship between the SIN and MOR pathways, which is important for completion of cytokinesis and coordination of cytoskeletal remodeling at the mitosis-to-interphase transition.</jats:p
Identification of SIN Pathway Targets Reveals Mechanisms of Crosstalk between NDR Kinase Pathways
No full textSummaryThe septum initiation network (SIN) regulates multiple functions during late mitosis to ensure successful completion of cytokinesis in Schizosaccharomyces pombe. One mechanism by which the SIN promotes cytokinesis is by inhibiting a competing polarity pathway called the MOR [1], which is required for initiation of polarized growth following completion of cytokinesis [2]. Mutual antagonism between the two NDR kinase pathways, SIN and MOR, is required to coordinate cytoskeletal rearrangements during the mitosis-interphase transition. To determine how the SIN regulates the MOR pathway, we developed a proteomics approach that allowed us to identify multiple substrates of the SIN effector kinase Sid2, including the MOR pathway components Nak1 kinase and an associated protein, Sog2. We show that Sid2 phosphorylation of Nak1 causes removal of Nak1 from the spindle pole bodies, which may both relieve Nak1 inhibition of the SIN and block MOR signaling by preventing interaction of Nak1 with the scaffold protein Mor2. Because the SIN and MOR are conserved in mammalian cells (Hippo and Ndr1/2 pathways, respectively), this work may provide important insight into how the activities of these essential pathways are coordinated
