Principles of organelle positioning in motile and non-motile cells

Kroll, Janina; Renkawitz, Jörg

doi:10.1038/s44319-024-00135-4

Cited by 4 publications

(4 citation statements)

References 186 publications

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“…2a). Given that DCs belong to the class of migrating cells that employ an amoeboid migration mode that is characterized by low-adhesiveness to the substrate and frontward positioning of the nucleus towards the cellular protrusion 3,22 , this even more frontward positioning of the parasitic cargo in relation to the host nucleus was highly unexpected. Notably, quantification of parasite positioning in relation to the parasite stage revealed that large parasitic 8- and 16-stage cargos particularly frequently positioned in front of the host nucleus (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To identify the forces that move the bulky parasitic cargo intracellularly, we targeted key cytoskeletal force generators within the host cell. Host cells position specific sets of their organelles by forces derived from the microtubule cytoskeleton and its motors 3 , including the pulling of the large and bulky nucleus in mesenchymal migrating cells 23 . However, the above-described positioning of Toxoplasma gondii parasites within DCs far frontward of the microtubule organizing center rather argued against a mechanism that employs microtubule forces to pull the bulky parasitic cargo.…”

Section: Resultsmentioning

confidence: 99%

“…After 2 min plasma cleaner the microchannels were flooded with imaging medium, and equilibrated in the cell culture incubator. 0.625 µg/ml CCL19 were loaded into one hole and 50x10 3 infected and stained dendritic cells in the other hole. Imaging was started as soon as the first cells entered into the microchannels.…”

Section: Methodsmentioning

confidence: 99%

“…Mammalian cells are equipped with dynamic cytoskeletal structures that provide forces for cell shape dynamics, cell motility, organelle positioning, and intracellular transport 1–3 . Intracellular pathogens can hijack these forces generated by the host cell to (i) facilitate their uptake, (ii) drive their intracellular motility, or (iii) prevent their degradation 4 .…”

Section: Introductionmentioning

confidence: 99%

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Hijacked Immune Cells Traverse Microenvironmental Barriers by Positioning and Pushing their Intracellular Parasite Cargo

Ruiz-Fernandez,

Jiang,

Mortazavi

et al. 2024

Preprint

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Intracellular pathogens hijack the cytoskeletal networks of their host cells to facilitate their uptake, drive their intracellular motility, or prevent their degradation. While many underlying principles have been explored during host cell infections by intracellular bacteria like Listeria, Chlamydia, or Shigella, it remains less well understood how large eukaryotic intracellular parasites like Toxoplasma gondii exploit the host cytoskeleton. In particular, how Toxoplasma achieves its transport within highly motile immune cells remains largely unknown despite its large intracellular size. Here, we discover that Toxoplasma gondii hijacks host myosin forces for translocation through microenvironmental barriers along immune cell migration paths. Using highly defined micro-engineered migration paths and dendritic cells as a highly motile immune cell model, we reveal that large parasitic cargos acquire a surprising intracellular position frontward of the host nucleus and microtubule-organizing center. This frontward localization of parasitic cargos depends on microenvironmental confinement and host myosin activity. We identify that the parasite cargos cause high contractility within their motile host cells mediated by host myosin-II, thereby facilitating their squeezing and deformation to enable transversal through confining microenvironments. Our findings establish parasitic hijacking of myosin forces as a novel principle of how parasites exploit host cytoskeletal networks.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hijacked Immune Cells Traverse Microenvironmental Barriers by Positioning and Pushing their Intracellular Parasite Cargo

Ruiz-Fernandez,

Jiang,

Mortazavi

et al. 2024

Preprint

Self Cite

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The endoplasmic reticulum as an active liquid network

Scott,

Steen,

Huber

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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The peripheral endoplasmic reticulum (ER) forms a dense, interconnected, and constantly evolving network of membrane-bound tubules in eukaryotic cells. While individual structural elements and the morphogens that stabilize them have been described, a quantitative understanding of the dynamic large-scale network topology remains elusive. We develop a physical model of the ER as an active liquid network, governed by a balance of tension-driven shrinking and new tubule growth. This minimalist model gives rise to steady-state network structures with density and rearrangement timescales predicted from the junction mobility and tubule spawning rate. Several parameter-independent geometric features of the liquid network model are shown to be representative of ER architecture in live mammalian cells. The liquid network model connects the timescales of distinct dynamic features such as ring closure and new tubule growth in the ER. Furthermore, it demonstrates how the steady-state network morphology on a cellular scale arises from the balance of microscopic dynamic rearrangements.

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The Endoplasmic Reticulum as an Active Liquid Network

Scott,

Steen,

Huber

et al. 2024

Preprint

View full text Add to dashboard Cite

The peripheral endoplasmic reticulum (ER) forms a dense, interconnected, and constantly evolving network of membrane-bound tubules in eukaryotic cells. While individual structural elements and the morphogens that stabilize them have been described, a quantitative understanding of the dynamic large-scale network topology remains elusive. We develop a physical model of the ER as an active liquid network, governed by a balance of tension-driven shrinking and new tubule growth. This minimalist model gives rise to steady-state network structures with density and rearrangement timescales predicted from the junction mobility and tubule spawning rate. Several parameter-independent geometric features of the liquid network model are shown to be representative of ER architecture in live mammalian cells. The liquid network model connects the time-scales of distinct dynamic features such as ring closure and new tubule growth in the ER. Furthermore, it demonstrates how the steady-state network morphology on a cellular scale arises from the balance of microscopic dynamic rearrangements.

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Principles of organelle positioning in motile and non-motile cells

Cited by 4 publications

References 186 publications

Hijacked Immune Cells Traverse Microenvironmental Barriers by Positioning and Pushing their Intracellular Parasite Cargo

Hijacked Immune Cells Traverse Microenvironmental Barriers by Positioning and Pushing their Intracellular Parasite Cargo

The endoplasmic reticulum as an active liquid network

The Endoplasmic Reticulum as an Active Liquid Network

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