A comprehensive model to predict mitotic division in budding yeasts

Sutradhar, Sabyasachi; Yadav, Vikas; Sridhar, Shreyas; Sreekumar, Lakshmi; Bhattacharyya, Dibyendu; Ghosh, Santanu; Paul, Raja; Sanyal, Kaustuv

doi:10.1091/mbc.e15-04-0236

Cited by 24 publications

(84 citation statements)

References 78 publications

(103 reference statements)

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“…MTs are the key regulator of the 'search & capture' process and capture the target contact sites for successive cargo transport or serving as ropes for the molecular motors on which they can sit and pull the MTs facilitating a number of cellular functions like nuclear migration in budding yeast (43), spindle positioning in C. elegans embryos (44), centrosome positioning in interphase cells (45,46), orientation of cortical MT array in plant cells (47), and nuclear-positioning in fission yeast facilitated by the formation of parallel microtubule bundles (26,48). Moreover, in certain yeast species, such as C. neoformans, MT mediated capture and subsequent aggregation of the MTOCs organizes the pre-mitotic assembly of spindle pole body (SPB) (49). Likewise, reassembly of Golgi via the concentrated effort of centrosomal MTs and the Golgi driven MTs also thought to rely on a 'search-capture' hypothesis (50).…”

Section: Introductionmentioning

confidence: 99%

Search and Capture Efficiency of Dynamic Microtubules for Centrosome Relocation during IS Formation

Sarkar

Rieger

Paul

2019

Biophysical Journal

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Upon contact with antigen presenting cells (APCs) cytotoxic T lymphocytes (T cells) establish a highly organized contact zone denoted as immunological synapse (IS). The formation of the IS implies relocation of the microtubule organizing center (MTOC) towards the contact zone, which necessitates a proper connection between MTOC and IS via dynamic microtubules (MTs). The efficiency of the MTs finding the IS within relevant time scale is, however, still illusive. We investigate how MTs search the three-dimensional constrained cellular volume for the IS and bind upon encounter to dynein anchored at the IS cortex. The search efficiency is estimated by calculating the time required for the MTs to reach the dynein-enriched region of the IS. In this study, we develop simple mathematical and numerical models incorporating relevant components of a cell and propose an optimal search strategy. Using the mathematical model, we have quantified the average search time for a wide range of model parameters and proposed an optimized set of values leading to the minimum capture time. Our results show that search times are minimal when the IS formed at the nearest or at the farthest sites on the cell surface, with respect to the perinuclear MTOC. The search time increases monotonically away from these two specific sites and are maximal at an intermediate position near the equator of the cell. We observed that search time strongly depends on the number of searching MTs and distance of the MTOC from the nuclear surface.

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Section: Introductionmentioning

confidence: 99%

Search and Capture Efficiency of Dynamic Microtubules for Centrosome Relocation during IS Formation

Sarkar

Rieger

Paul

2019

Biophysical Journal

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“…Such depolymerization while walking on the MTs could compensate for an important source of mechanics in spindle positioning based on MT pushing by polymerization seen in vitro (Dogterom et al, 2005;Dogterom and Yurke, 1997). The most recent modeling study of nuclear positioning in yeast based on MT-motor mechanics is limited by the fact of continuum assumptions about motors and MTs (Sutradhar et al, 2015), while the number of motors and MTs seen in experiment are small in number, and likely to be subject to fluctuations. This suggests the a model that takes into account individual MTs and single motor mechanics is required for an improved understanding of the biophysical basis of nuclear positioning in S. cerevisiae mitosis.…”

Section: Introductionmentioning

confidence: 99%

Dynein collective behavior in mitotic nuclear positioning of Saccharomyces cerevisiae

Jain

Khetan

Palani

et al. 2020

Preprint

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Positioning the nucleus at the bud-neck prior during Saccharomyces cerevisiae mitosis during anaphase involves pulling forces of cytoplasmic dynein localized in the daughter cell. While genetic analysis has revealed a complex network positioning the nucleus, quantification of the forces acting on the nucleus and dyneins numbers driving the process has remained difficult. In order to better understand the role of motor-microtubule mechanics during nuclear positioning and the role of dynein, we have used a computational model of nuclear mobility in S. cerevisiae and reconciled it to the mobility of labelled spindle pole bodies (SPBs) measured by quantifying fluorescence microscopy time-series. We model the apparent random-walk mobility of SPBs by combining diffusion of the nucleus and active pushing of MTs at the cell membrane. By minimizing the deviation between tracks of fluorescently tagged SPBs and simulations, we estimate the effective cytoplasmic viscosity to be 0.5 Pa s. The directed transport of nuclei during the budding process is similarly quantified by tracking the daughter SPB (SPB-D) in experiment. Using force-balance, we find 2 to 8 motors are required to pull the nucleus to the bud-neck. Simulations of the cytoplasmic MT (cMT) 'search and capture' by dynein suggest single motor binding is followed by a rapid saturation of number of bound motors. The short time and length of MT interactions with the cortex and minimal collective dynein force required, predict a functional role for dynein clustering in nuclear positioning.

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“…However, the NE never breaks down, leading to closed mitosis [23,24]. In contrast to S. cerevisiae, where the SPB being the only MTOC, several MTOCs are present in the basidiomycete budding yeast C. neoformans during interphase [14,25,26] (Fig 2A). Moreover, it undergoes semi-open mitosis marked by the transient breakdown/rupture of NE during metaphase to anaphase transition [15,27].…”

Section: Introductionmentioning

confidence: 99%

“…The clustering of KTs into a single punctum and the clustering of MTOCs into a single SPB happen concomitantly (Fig 2A-2C). (c) In S. cerevisiae, prior to the chromosome segregation, the nucleus migrates to the proximity of mother-daughter bud neck junction [14,16,31,32]. In C. neoformans, the sequence of events characterizing nuclear migration before the division is somewhat different from those of S. cerevisiae.…”

Section: Introductionmentioning

confidence: 99%

“…First, the nucleus entirely moves to the daughter bud (S1 Fig). Second, the SPB duplication takes place either in the daughter bud or when the nucleus is migrated close to the bud-neck junction (namely the septin ring) as depicted in Fig 2A, Fig 2C. Subsequently, SPB biorientation, spindle formation, and localization of the spindle structure inside the daughter bud near the septin ring pave the way for proper division [14][15][16]. Interestingly, the features of having multiple MTOCs and nuclear division in the daughter bud are also characteristics of another basidiomycete yeast, Ustilago maydis [33].…”

Section: Introductionmentioning

confidence: 99%

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Mechanics of MTOC clustering and spindle positioning in budding yeast Cryptococcus neoformans

Chatterjee

Som

Varshney

et al. 2019

Preprint

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The mitotic spindle formation in pathogenic budding yeast, Cryptococcus neoformans, depends on multitudes of intertwined interactions primarily between kinetochores, microtubules (MT), spindle pole bodies (SPBs) and various molecular motors. Prior to spindle formation microtubule organizing centers (MTOCs), embedded on the outer nuclear envelope (NE), coalesce into a single SPB.We propose a 'grow-and-catch' model, in which cytoplasmic MTs (cMTs) nucleated by MTOCs grow and catch each other, to facilitate MTOC clustering. Our quantitative modeling analysis supported by experiments, for the first time, identifies multiple redundant mechanisms mediated by cMT-cell cortex interactions via dynein and Bim1, act in synchrony for timely clustering of MTOCs. Implementing a similar stochastic model of 'grow-and-catch' kinetochores, here we demonstrate that pre-clustered kinetochores and highly biased MTs are a pre-requisite for timely capture of duplicated kinetochores. Further, in the absence of an error correction mechanism, the mitotic division culminates in a biased and asymmetric distribution of the nuclear mass. The model predicts that either a marginal delay in MT nucleation from the daughter SPB or an enhanced MT nucleation from the mother SPB can independently account for the asymmetry as observed in the experiment.

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A comprehensive model to predict mitotic division in budding yeasts

Cited by 24 publications

References 78 publications

Search and Capture Efficiency of Dynamic Microtubules for Centrosome Relocation during IS Formation

Search and Capture Efficiency of Dynamic Microtubules for Centrosome Relocation during IS Formation

Dynein collective behavior in mitotic nuclear positioning of Saccharomyces cerevisiae

Mechanics of MTOC clustering and spindle positioning in budding yeast Cryptococcus neoformans

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