For cells to develop long-range forces and carry materials to the periphery, the microtubule and organelle-rich region at the center of the cell-the endoplasm-needs to extend to near the cell edge. Depletion of the actin cross-linking protein filamin A (FlnA) causes a collapse of the endoplasm into a sphere around the nucleus of fibroblasts and disruption of matrix adhesions, indicating that FlnA is involved in endoplasmic spreading and adhesion growth. Here, we report that treatment with the calpain inhibitor N-[N-(N-acetyl-l-leucyl)-l-leucyl]-l-norleucine (ALLN) restores endoplasmic spreading as well as focal adhesion (FA) growth on fibronectin-coated surfaces in a Fln-depleted background. Addback of calpain-uncleavable talin, not full-length talin, achieves a similar effect in Fln-depleted cells and indicates a crucial role for talin in endoplasmic spreading. Because FA maturation involves the vimentin intermediate filament (vIF) network, we also examined the role of vIFs in endoplasmic spreading. Wild-type cells expressing a vimentin variant incapable of polymerization exhibit deficient endoplasmic spreading as well as defects in FA growth. ALLN treatment restores FA growth despite the lack of vIFs but does not restore endoplasmic spreading, implying that vIFs are essential for endoplasm spreading. Consistent with that hypothesis, vIFs are always displaced from adhesions when the endoplasm does not spread. In Fln-depleted cells, vIFs extend beyond adhesions, nearly to the cell edge. Finally, inhibiting myosin II-mediated contraction blocks endoplasmic spreading and adhesion growth. Thus we propose a model in which myosin II-mediated forces and coalescence of vIFs at mature FAs are required for endoplasmic spreading.
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http://dx.doi.org/10.1091/mbc.E12-05-0377 | DOI Listing |
J Cell Biol
March 2025
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Upon invasion into the host cell, a subset of bacterial pathogens resides exclusively in the cytosol. While previous research revealed how they reshape the plasma membrane during invasion, subvert the immune response, and hijack cytoskeletal dynamics to promote their motility, it was unclear if these pathogens also interacted with the organelles in this crowded intracellular space. Here, we examined if the obligate intracellular pathogen Rickettsia parkeri interacts with the endoplasmic reticulum (ER), a large and dynamic organelle spread throughout the cell.
View Article and Find Full Text PDFmBio
January 2025
Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease Research, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
The unfolded protein response (UPR) is a cell-autonomous stress response aimed at restoring homeostasis due to the accumulation of misfolded proteins in the endoplasmic reticulum (ER). Viruses often hijack the host cell machinery, leading to an accumulation of misfolded proteins in the ER. The cell-autonomous UPR is the immediate response of an infected cell to this stress, aiming to restore normal function by halting protein translation, degrading misfolded proteins, and activating signaling pathways that increase the production of molecular chaperones.
View Article and Find Full Text PDFJ Virol
December 2024
Citrus Research and Education Center, University of Florida, Lake Alfred, Florida, USA.
Unlabelled: transmits Liberibacter asiaticus (CLas) between citrus plants which causes the expression of huanglongbing disease in citrus. flavi-like virus (DcFLV) co-occurs intracellularly with CLas in populations in the field. However, the impact(s) of DcFLV presence on the insect vector and its interaction with the CLas phytopathogen remain unclear.
View Article and Find Full Text PDFACS Infect Dis
January 2025
Global Health R&D of the healthcare business of Merck KGaA, Darmstadt, Germany, Ares Trading S.A., (an affiliate of Merck KGaA, Darmstadt, Germany, Route de Crassier 1, 1262 Eysins, Switzerland.
New antimalarial combination therapies with novel modes of action are required to counter the emergence and spread of drug resistance against existing therapeutics. Here, we present a study to evaluate the preventive activity of a combination of clinical antimalarial drug candidates, cabamiquine and ganaplacide, that have multistage activity against the liver and blood stages of infection. Cabamiquine (DDD107498, M5717) inhibits parasite protein synthesis, and ganaplacide (KAF156) inhibits protein trafficking, blocks the establishment of new permeation pathways, and causes endoplasmic reticulum expansion.
View Article and Find Full Text PDFJ Microsc
December 2024
Biology Department and the Molecular and Environmental Plant Sciences Program, Texas A&M University, College Station, Texas, USA.
The endoplasmic reticulum (ER) forms contact sites with the chloroplast. Exposing contact sites that contain both the chloroplast and the ER to localised high-fluence, wavelength specific, 405 nm violet light, hereinafter referred to as photostimulation, induces multiple, potentially interacting intra- and intercellular responses. The responses vary depending on the tissue type of the cell and the chloroplast.
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