Microtubule stability is known to be governed by a stabilizing GTP/GDP-Pi cap, but the exact relation between growth velocity, GTP hydrolysis, and catastrophes remains unclear. We investigate the dynamics of the stabilizing cap through in vitro reconstitution of microtubule dynamics in contact with microfabricated barriers, using the plus-end binding protein GFP-EB3 as a marker for the nucleotide state of the tip. The interaction of growing microtubules with steric objects is known to slow down microtubule growth and accelerate catastrophes. We show that the lifetime distributions of stalled microtubules, as well as the corresponding lifetime distributions of freely growing microtubules, can be fully described with a simple phenomenological 1D model based on noisy microtubule growth and a single EB3-dependent hydrolysis rate. This same model is furthermore capable of explaining both the previously reported mild catastrophe dependence on microtubule growth rates and the catastrophe statistics during tubulin washout experiments.
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http://dx.doi.org/10.1016/j.bpj.2024.11.3314 | DOI Listing |
Heliyon
December 2024
Department of Medical Rehabilitation, School of Nursing, Jilin University, 965 Xinjiang Street, Chaoyang District, Changchun, 130021, China.
Cervical squamous cell carcinoma (CESC) is a common cancer in women. Despite advancements in early diagnosis through high-risk human papillomavirus (HPV) screening, challenges remain in predicting and treating the disease. Hence, the identification of novel biomarkers for prognosis and therapeutic targets is crucial.
View Article and Find Full Text PDFOpen Life Sci
December 2024
Institute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany.
Cell polarity is crucial in neurons, characterized by distinct axonal and dendritic structures. Neurons generally have one long axon and multiple shorter dendrites, marked by specific microtubule (MT)-associated proteins, e.g.
View Article and Find Full Text PDFJ Cell Mol Med
January 2025
Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
The development of efficient platforms for the evaluation of anti-angiogenic agents is critical in advancing cancer therapeutics. In this study, we exploited an ultrabright semiconducting polymer dots (Pdots) integrating with a three-dimensional (3D) near-infrared-II (NIR-II) fluorescence imaging system designed to assess the efficacy of potent anti-angiogenic agents PX-478 and BPR0C261 in an oral squamous cell carcinoma (OSCC) tumour model, which depends on angiogenesis for dissemination. PX-478, a hypoxia-inducible factor-1α (HIF-1α) inhibitor, and BPR0C261, a microtubule-disrupting agent, were administrated into tumour-bearing mice established using murine MTCQ1 tongue cancer cells through intraperitoneal injection and oral gavage, respectively.
View Article and Find Full Text PDFJ Nucl Med
January 2025
Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts;
Radionuclides used for imaging and therapy can show high molecular specificity in the body with appropriate targeting ligands. We hypothesized that local energy delivered by molecularly targeted radionuclides could chemically activate prodrugs at disease sites while avoiding activation in off-target sites of toxicity. As proof of principle, we tested whether this strategy of radionuclide-induced drug engagement for release (RAiDER) could locally deliver combined radiation and chemotherapy to maximize tumor cytotoxicity while minimizing off-target exposure to activated chemotherapy.
View Article and Find Full Text PDFJ Cell Physiol
January 2025
Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China.
Cervical cancer remains a significant global health concern. KIF18A, a kinesin motor protein regulating microtubule dynamics during mitosis, is frequently overexpressed in various cancers, but its regulatory mechanisms are poorly understood. This study investigates KIF18A's role in cervical cancer and its regulation by the JNK1/c-Jun signaling pathway.
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