Browsing by Author "Cabeza, Carolina"
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Item c-Jun N-terminal kinase (JNK)- dependent internalization and Rab5-dependent endocytic sorting mediate long-distance retrograde neuronal death induced by axonal BDNF-p75 signaling(2019) Escudero, Claudia; Cabeza, Carolina; Moya-Alvarado, Guillermo; Maloney, M. T.; Flores, C. M.; Wu, Chengbiao; Court, Felipe A.; Mobley, William; Bronfman, Francisca C.During the development of the sympathetic nervous system, signals from tropomyosin-related kinase receptors (Trks) and p75 neurotrophin receptors (p75) compete to regulate survival and connectivity. During this process, nerve growth factor (NGF)- TrkA signaling in axons communicates NGF-mediated trophic responses in signaling endosomes. Whether axonal p75 signaling contributes to neuronal death and how signaling endosomes contribute to p75 signaling has not been established. Using compartmentalized sympathetic neuronal cultures (CSCGs) as a model, we observed that the addition of BDNF to axons increased the transport of p75 and induced death of sympathetic neurons in a dynein-dependent manner. In cell bodies, internalization of p75 required the activity of JNK, a downstream kinase mediating p75 death signaling in neurons. Additionally, the activity of Rab5, the key GTPase regulating early endosomes, was required for p75 death signaling. In axons, JNK and Rab5 were required for retrograde transport and death signaling mediated by axonal BDNF-p75 in CSCGs. JNK was also required for the proper axonal transport of p75-positive endosomes. Thus, our findings provide evidence that the activation of JNK by p75 in cell bodies and axons is required for internalization to a Rab5-positive signaling endosome and the further propagation of p75-dependent neuronal death signals.Publication Capture and detection of extracellular vesicles derived from human breast cancer cells using a 3D self-assembled nanostructured SiO2 microfluidic chip(2025) Cabeza, Carolina; Rojas, Felipe; Lobos, Lorena; Lemaitre, Dominique; Villena, Juan; Cordero, María; Hassan, Natalia; Ortiz, RinaBackground: Tumor-derived extracellular vesicles offer a minimally invasive approach to evaluate tumor progression and metastasis. However, detecting biomarkers, such as extracellular vesicles in body fluids during the early stages of disease, remains a significant challenge. Conventional methods like ultracentrifugation-based isolation or Western blot protein quantification are time-consuming, require large sample volumes, and offer low yield and sensitivity. Therefore, the development of new biosensors for the specific and efficient analysis of tumor extracellular vesicles is urgently needed. Methods: Microfluidic devices provide extraordinary benefits for bioanalysis, offering a large surface area for the contact between target molecules and the biosensor, significantly enhancing the specificity, efficiency, and speed. These devices also enable nanoscale and microscale work using reduced sample volumes. In this study, we developed a three-dimensional self-assembled SiO2-based nanostructured microfluidic chip, bioconjugated with specific antibodies targeting exosomal markers for the selective capture of CD63- and CD81-positive extracellular vesicles from breast cancer-derived conditioned cell culture media. Results: The three-dimensional SiO2-based microfluidic chip effectively captured extracellular vesicles expressing CD63 and CD81 antigens from breast cancer cell culture media. This evidence demonstrates the potential of this platform to detect extracellular vesicles as biomarkers for cancer, providing a specific and efficient, non-invasive approach for cancer diagnostics. Conclusions: This study highlights the potential application of three-dimensional SiO2-based microfluidic chips for detecting extracellular vesicles as a non-invasive liquid biopsy tool for breast cancer. The findings show a specific and efficient device as an alternative to conventional biomarker detection techniques.