Endoplasmic reticulum network heterogeneity guides diffusive transport and kinetics

Scott, Zubenelgenubi C.; Koning, Katherine; Cohen, Lorna; Westrate, Laura M.; Koslover, Elena F.

doi:10.1016/j.bpj.2023.06.022

Cited by 7 publications

(3 citation statements)

References 69 publications

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“…4 F ). These results are consistent with prior work demonstrating that structural heterogeneity of the ER can play an important role in modulating transport through the network ( 83 ).…”

Section: Resultssupporting

confidence: 93%

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca ²⁺ signals

Crapart,

Scott,

Konno

et al. 2024

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

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The endoplasmic reticulum (ER) forms an interconnected network of tubules stretching throughout the cell. Understanding how ER functionality relies on its structural organization is crucial for elucidating cellular vulnerability to ER perturbations, which have been implicated in several neuronal pathologies. One of the key functions of the ER is enabling Ca 2 + signaling by storing large quantities of this ion and releasing it into the cytoplasm in a spatiotemporally controlled manner. Through a combination of physical modeling and live-cell imaging, we demonstrate that alterations in ER shape significantly impact its ability to support efficient local Ca 2 + releases, due to hindered transport of luminal content within the ER. Our model reveals that rapid Ca 2 + release necessitates mobile luminal buffer proteins with moderate binding strength, moving through a well-connected network of ER tubules. These findings provide insight into the functional advantages of normal ER architecture, emphasizing its importance as a kinetically efficient intracellular Ca 2 + delivery system.

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“…4 F ). These results are consistent with prior work demonstrating that structural heterogeneity of the ER can play an important role in modulating transport through the network ( 83 ).…”

Section: Resultssupporting

confidence: 93%

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca ²⁺ signals

Crapart,

Scott,

Konno

et al. 2024

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…4f). These results are consistent with prior work demonstrating that structural heterogeneity of the ER can play an important role in modulating transport through the network (83).…”

Section: Resultssupporting

confidence: 93%

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca²⁺signals

Scott

Konno

et al. 2023

Preprint

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The endoplasmic reticulum (ER) forms an interconnected network of tubules stretching throughout the cell. Understanding how ER functionality relies on its structural organization is crucial for elucidating cellular vulnerability to ER perturbations, which have been implicated in several neuronal pathologies. One of the key functions of the ER is enabling Ca2+ signalling by storing large quantities of this ion and releasing it into the cytoplasm in a spatiotemporally controlled manner. Through a combination of physical modeling and live-cell imaging, we demonstrate that alterations in ER shape significantly impact its ability to support efficient local Ca2+ releases, due to hindered transport of luminal content within the ER. Our model reveals that rapid Ca2+ release necessitates mobile luminal buffer proteins with moderate binding strength, moving through a well-connected network of ER tubules. These findings provide insight into the functional advantages of normal ER architecture, emphasizing its importance as a kinetically efficient intracellular Ca2+ delivery system.

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“…Many more changes are occurring inside the cell. Inside cells, there is a network structure called the endoplasmic reticulum (ER), which consists of flat membranes and is involved in protein synthesis and transport [189]. Like other coronaviruses, SARS-CoV-2 inflates its long, thin endoplasmic reticulum like a soap bubble into a spherical double-membrane vesicle (DMV), which acts as a "hidden" place where viral RNA is replicated and translated without being detected by the innate immune system within the cell [190,191].…”

Section: Intracellular Changes With Virus Infectionsmentioning

confidence: 99%

Understanding the Molecular Actions of Spike Glycoprotein in SARS-CoV-2 and Issues of a Novel Therapeutic Strategy for the COVID-19 Vaccine

Matsuzaka,

Yashiro

2024

BioMedInformatics

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In vaccine development, many use the spike protein (S protein), which has multiple “spike-like” structures protruding from the spherical structure of the coronavirus, as an antigen. However, there are concerns about its effectiveness and toxicity. When S protein is used in a vaccine, its ability to attack viruses may be weak, and its effectiveness in eliciting immunity will only last for a short period of time. Moreover, it may cause “antibody-dependent immune enhancement”, which can enhance infections. In addition, the three-dimensional (3D) structure of epitopes is essential for functional analysis and structure-based vaccine design. Additionally, during viral infection, large amounts of extracellular vesicles (EVs) are secreted from infected cells, which function as a communication network between cells and coordinate the response to infection. Under conditions where SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) molecular vaccination produces overwhelming SARS-CoV-2 spike glycoprotein, a significant proportion of the overproduced intracellular spike glycoprotein is transported via EVs. Therefore, it will be important to understand the infection mechanisms of SARA-CoV-2 via EV-dependent and EV-independent uptake into cells and to model the infection processes based on 3D structural features at interaction sites.

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Endoplasmic reticulum network heterogeneity guides diffusive transport and kinetics

Cited by 7 publications

References 69 publications

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca ²⁺ signals

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca ²⁺ signals

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca²⁺signals

Understanding the Molecular Actions of Spike Glycoprotein in SARS-CoV-2 and Issues of a Novel Therapeutic Strategy for the COVID-19 Vaccine

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Endoplasmic reticulum network heterogeneity guides diffusive transport and kinetics

Cited by 7 publications

References 69 publications

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca 2+ signals

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca 2+ signals

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca2+signals

Understanding the Molecular Actions of Spike Glycoprotein in SARS-CoV-2 and Issues of a Novel Therapeutic Strategy for the COVID-19 Vaccine

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Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca ²⁺ signals

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca ²⁺ signals

Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca²⁺signals