scholarly journals Separate to operate: the centriole-free inner core of the centrosome regulates the assembly of the intranuclear spindle in Toxoplasma gondii

2022 ◽  
Author(s):  
Ramiro Tomasina ◽  
Érica S Martins-Duarte ◽  
Philippe Bastin ◽  
Mathieu Gissot ◽  
Maria E Francia
Keyword(s):  
Cell Division ◽  
Toxoplasma Gondii ◽  
Mitotic Spindle ◽  
Inner Core ◽  
Cell Formation ◽  
Outer Core ◽  
Structural Defects ◽  
Microtubule Organizing Center ◽  
Pericentriolar Material

Centrosomes are the main microtubule-organizing center of the cell. They are normally formed by two centrioles, embedded in a cloud of proteins known as pericentriolar material. The PCM ascribes centrioles with their microtubule nucleation capacity. Toxoplasma gondii, the causative agent of toxoplasmosis, divides by endodyogeny. Successful cell division is critical for pathogenesis. The centrosome, plays central roles in orchestrating the temporal and physical coordination of major organelle segregation and daughter cell formation. The T. gondii centrosome is formed by two domains; an outer core, distal from the nucleus, and an inner core, proximal to the nucleus. This dual organization has been proposed to underlie T. gondii’s cell division plasticity. However, the role of the inner core remains undeciphered. Here, we focus on the role of its only known molecular marker; TgCEP250L1. We show that upon conditional degradation of TgCEP250L1, parasites exhibit nuclear segregation defects, whilst normally forming daughter cells. In addition, the centrioles, disconnect from the nucleus. We explore the structural defects underlying these phenotypes by high resolution microscopy. We show that TgCEP250L1’s location is dynamic and encompasses the formation of the mitotic spindle. Moreover, we show that in the absence of TgCEP250L1, the microtubule binding protein TgEB1, fails to translocate from the nucleus to the mitotic spindle, while polyploid nuclei accumulate. Overall, our data supports a model in which the inner core of the T. gondii centrosome critically participates in cell division by directly impacting the formation or stability of the mitotic spindle.

scholarly journals TgCep250 is dynamically processed through the division cycle and is essential for structural integrity of the Toxoplasma centrosome

2019 ◽  
Vol 30 (10) ◽  
pp. 1160-1169 ◽  
Author(s):  
Chun-Ti Chen ◽  
Marc-Jan Gubbels
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Toxoplasma Gondii ◽  
Structural Integrity ◽  
Inner Core ◽  
Coiled Coil ◽  
Outer Core ◽  
Proteolytic Processing ◽  
Mother And Daughter ◽  
Spatiotemporal Localization

The apicomplexan centrosome has a unique bipartite structure comprising an inner and outer core responsible for the nuclear cycle (mitosis) and budding cycles (cytokinesis), respectively. Although these two cores are always associated, they function independently to facilitate polyploid intermediates in the production of many progeny per replication round. Here, we describe the function of a large coiled-coil protein in Toxoplasma gondii, TgCep250, in connecting the two centrosomal cores and promoting their structural integrity. Throughout the cell cycle, TgCep250 localizes to the inner core but, associated with proteolytic processing, is also present on the outer core during the onset of cell division. In the absence of TgCep250, stray centrosome inner and outer core foci were observed. The detachment between centrosomal inner and outer cores was found in only one of the centrosomes during cell division, indicating distinct states of mother and daughter centrosomes. In mammals, Cep250 processing is required for centrosomal splitting and is mediated by Nek phopsphorylation. However, we show that neither the nonoverlapping spatiotemporal localization of TgNek1 and TgCep250 nor the distinct phenotypes upon their respective depletion support conservation of this mechanism in Toxoplasma. In conclusion, TgCep250 has a tethering function tailored to the unique bipartite centrosome in the Apicomplexa.

3. Minerals and the interior of the Earth

2014 ◽  
Author(s):  
David Vaughan
Keyword(s):  
Upper Mantle ◽  
Lower Mantle ◽  
Plate Tectonics ◽  
Inner Core ◽  
Indirect Evidence ◽  
Outer Core ◽  
The Earth ◽  
Granite Formation ◽  
Temperature And Pressure

‘Minerals and the interior of the Earth’ looks at the role of minerals in plate tectonics during the processes of crystallization and melting. The size and range of minerals formed are dependent on the temperature and pressure of the magma during its movement through the crust. The evolution of the continental crust also involves granite formation and processes of metamorphism. Our understanding of the interior of the Earth is based on indirect evidence, mainly the study of earthquake waves. The Earth consists of concentric shells: a solid inner core; liquid outer core; a solid mantle divided into a lower mantle, a transition zone, and an upper mantle; and then the outer rigid lithosphere.

scholarly journals Stability and function of a putative microtubule-organizing center in the human parasite Toxoplasma gondii

2017 ◽  
Vol 28 (10) ◽  
pp. 1361-1378 ◽  
Author(s):  
Jacqueline M. Leung ◽  
Yudou He ◽  
Fangliang Zhang ◽  
Yu-Chen Hwang ◽  
Eiji Nagayasu ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Structural Integrity ◽  
Lytic Cycle ◽  
Host Cells ◽  
Structural Defects ◽  
Cortical Microtubules ◽  
Microtubule Organizing Center ◽  
Polar Ring ◽  
Human Parasite ◽  
Organizing Center

The organization of the microtubule cytoskeleton is dictated by microtubule nucleators or organizing centers. Toxoplasma gondii, an important human parasite, has an array of 22 regularly spaced cortical microtubules stemming from a hypothesized organizing center, the apical polar ring. Here we examine the functions of the apical polar ring by characterizing two of its components, KinesinA and APR1, and show that its putative role in templating can be separated from its mechanical stability. Parasites that lack both KinesinA and APR1 (ΔkinesinAΔapr1) are capable of generating 22 cortical microtubules. However, the apical polar ring is fragmented in live ΔkinesinAΔapr1 parasites and is undetectable by electron microscopy after detergent extraction. Disintegration of the apical polar ring results in the detachment of groups of microtubules from the apical end of the parasite. These structural defects are linked to a diminished ability of the parasite to move and invade host cells, as well as decreased secretion of effectors important for these processes. Together the findings demonstrate the importance of the structural integrity of the apical polar ring and the microtubule array in the Toxoplasma lytic cycle, which is responsible for massive tissue destruction in acute toxoplasmosis.

scholarly journals Impact of inner core rotation on outer core flow: the role of outer core viscosity

2004 ◽  
Vol 159 (1) ◽  
pp. 372-389 ◽  
Author(s):  
J. Y. Guo ◽  
P. M. Mathews ◽  
Z. X. Zhang ◽  
J. S. Ning
Keyword(s):  
Inner Core ◽  
Outer Core ◽  
Core Flow ◽  
Core Rotation ◽  
Inner Core Rotation

scholarly journals A Novel Actin-Related Protein Is Associated with Daughter Cell Formation in Toxoplasma gondii

2008 ◽  
Vol 7 (9) ◽  
pp. 1500-1512 ◽  
Author(s):  
Jennifer L. Gordon ◽  
Wandy L. Beatty ◽  
L. David Sibley
Keyword(s):  
Cell Division ◽  
Toxoplasma Gondii ◽  
Daughter Cell ◽  
Cell Formation ◽  
The Body ◽  
Apicomplexan Parasites ◽  
Daughter Cells ◽  
Membrane Complex ◽  
Transport Vesicles ◽  
Inner Membrane Complex

ABSTRACT Cell division in Toxoplasma gondii occurs by an unusual budding mechanism termed endodyogeny, during which twin daughters are formed within the body of the mother cell. Cytokinesis begins with the coordinated assembly of the inner membrane complex (IMC), which surrounds the growing daughter cells. The IMC is compiled of both flattened membrane cisternae and subpellicular filaments composed of articulin-like proteins attached to underlying singlet microtubules. While proteins that comprise the elongating IMC have been described, little is known about its initial formation. Using Toxoplasma as a model system, we demonstrate that actin-like protein 1 (ALP1) is partially redistributed to the IMC at early stages in its formation. Immunoelectron microscopy localized ALP1 to a discrete region of the nuclear envelope, on transport vesicles, and on the nascent IMC of the daughter cells prior to the arrival of proteins such as IMC-1. The overexpression of ALP1 under the control of a strong constitutive promoter disrupted the formation of the daughter cell IMC, leading to delayed growth and defects in nuclear and apicoplast segregation. Collectively, these data suggest that ALP1 participates in the formation of daughter cell membranes during cell division in apicomplexan parasites.

The Role of the Centrosome in Development and Progression of Breast Cancer

2001 ◽  
Vol 7 (S2) ◽  
pp. 582-583
Author(s):  
W. Lingle ◽  
J. Salisbury ◽  
S. Barrett ◽  
V. Negron ◽  
C. Whitehead
Keyword(s):  
Mitotic Spindle ◽  
Mammalian Cells ◽  
Microtubule Organizing Center ◽  
Daughter Cells ◽  
Spindle Poles ◽  
Sister Chromatids ◽  
Close Proximity ◽  
Interphase Cells ◽  
Organizing Center

The centrosome is the major microtubule organizing center in most mammalian cells, and as such it determines the number, polarity, and spatial distribution of microtubules (MTs). Interphase MTs, together with actin and intermediate filaments, constitute the cell's cytoskeleton, which dynamically maintains cell polarity and tissue architecture. Interphase cells begin Gl of the cell cycle with one centrosome. During S phase, the centrosome duplicates concomitantly with DNA replication. Duplicated centrosomes usually remain in close proximity to one another until late G2, at which time they separate and then move during prophase to become the poles that organize the bipolar mitotic spindle. During the G2/M transition, interphase MTs depolymerize and a new population of highly dynamic mitotic MTs are nucleated at the spindle poles. The bipolar mitotic spindle apparatus constitutes the machinery that partitions and separates sister chromatids equally between two daughter cells.

scholarly journals Stability and function of a putative microtubule organizing center in the human parasite Toxoplasma gondii

2017 ◽  
Author(s):  
Jacqueline M. Leung ◽  
Yudou He ◽  
Fangliang Zhang ◽  
Yu-Chen Hwang ◽  
Eiji Nagayasu ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Structural Integrity ◽  
Lytic Cycle ◽  
Host Cells ◽  
Structural Defects ◽  
Cortical Microtubules ◽  
Microtubule Organizing Center ◽  
Polar Ring ◽  
Human Parasite ◽  
Organizing Center

ABSTRACTThe organization of the microtubule cytoskeleton is dictated by microtubule nucleators or organizing centers. Toxoplasma gondii, an important human parasite, has an array of 22 regularly spaced cortical microtubules stemming from a hypothesized organizing center, the apical polar ring. Here, we examine the functions of the apical polar ring by characterizing two of its components, KinesinA and APR1, and discovered that its putative role in templating can be separated from its mechanical stability. Parasites that lack both KinesinA and APR1 (ΔkinesinAΔapr1) are capable of generating 22 cortical microtubules. However, the apical polar ring is fragmented in live ΔkinesinAΔapr1 parasites, and is undetectable by electron microscopy after detergent extraction. Disintegration of the apical polar ring results in the detachment of groups of microtubules from the apical end of the parasite. These structural defects are linked to a diminished ability of the parasite to move and to invade host cells, as well as decreased secretion of effectors important for these processes. Together, the findings demonstrate the importance of the structural integrity of the apical polar ring and the microtubule array in the Toxoplasma lytic cycle, which is responsible for massive tissue destruction in acute toxoplasmosis.

scholarly journals A centriole's subdistal appendages: contributions to cell division, ciliogenesis and differentiation

Open Biology ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 200399
Author(s):  
Nicole A. Hall ◽  
Heidi Hehnly
Keyword(s):  
Cell Division ◽  
Cell Differentiation ◽  
Final Stage ◽  
Eukaryotic Species ◽  
Chromosome Alignment ◽  
Cilia Formation ◽  
Mother Centriole ◽  
Pericentriolar Material ◽  
Daughter Centriole

The centrosome is a highly conserved structure composed of two centrioles surrounded by pericentriolar material. The mother, and inherently older, centriole has distal and subdistal appendages, whereas the daughter centriole is devoid of these appendage structures. Both appendages have been primarily linked to functions in cilia formation. However, subdistal appendages present with a variety of potential functions that include spindle placement, chromosome alignment, the final stage of cell division (abscission) and potentially cell differentiation. Subdistal appendages are particularly interesting in that they do not always display a conserved ninefold symmetry in appendage organization on the mother centriole across eukaryotic species, unlike distal appendages. In this review, we aim to differentiate both the morphology and role of the distal and subdistal appendages, with a particular focus on subdistal appendages.

Mitotic spindle morphogenesis: Ran on the microtubule cytoskeleton and beyond

2006 ◽  
Vol 34 (5) ◽  
pp. 716-721 ◽  
Author(s):  
B. Goodman ◽  
Y. Zheng
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Microtubule Assembly ◽  
Microtubule Organization ◽  
Spindle Matrix ◽  
Small G Protein ◽  
Important Regulator

Assembly and disassembly of the mitotic spindle are essential for both chromosome segregation and cell division. The small G-protein Ran has emerged as an important regulator of spindle assembly. In this review, we look at the role of Ran in different aspects of spindle assembly, including its effects on microtubule assembly dynamics and microtubule organization. In addition, we examine the possibility of a spindle matrix and the role Ran might play in such a structure.

scholarly journals A two-step mechanism for the inactivation of microtubule organizing center function at the centrosome

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Jérémy Magescas ◽  
Jenny C Zonka ◽  
Jessica L Feldman
Keyword(s):  
Cell Cycle ◽  
Mitotic Spindle ◽  
Outer Sphere ◽  
Microtubule Organizing Center ◽  
C Elegans ◽  
Mitotic Kinases ◽  
Pulling Forces ◽  
Organizing Center ◽  
Pericentriolar Material ◽  
Step Mechanism

The centrosome acts as a microtubule organizing center (MTOC), orchestrating microtubules into the mitotic spindle through its pericentriolar material (PCM). This activity is biphasic, cycling through assembly and disassembly during the cell cycle. Although hyperactive centrosomal MTOC activity is a hallmark of some cancers, little is known about how the centrosome is inactivated as an MTOC. Analysis of endogenous PCM proteins in C. elegans revealed that the PCM is composed of partially overlapping territories organized into an inner and outer sphere that are removed from the centrosome at different rates and using different behaviors. We found that phosphatases oppose the addition of PCM by mitotic kinases, ultimately catalyzing the dissolution of inner sphere PCM proteins at the end of mitosis. The nature of the PCM appears to change such that the remaining aging PCM outer sphere is mechanically ruptured by cortical pulling forces, ultimately inactivating MTOC function at the centrosome.

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