RESUMO
Reelin, a secreted glycoprotein, plays a crucial role in guiding neocortical neuronal migration, dendritic outgrowth and arborization, and synaptic plasticity in the adult brain. Reelin primarily operates through the canonical lipoprotein receptors apolipoprotein E receptor 2 (Apoer2) and very low-density lipoprotein receptor (Vldlr). Reelin also engages with non-canonical receptors and unidentified co-receptors; however, the effects of which are less understood. Using high-throughput tandem mass tag LC-MS/MS-based proteomics and gene set enrichment analysis, we identified both shared and unique intracellular pathways activated by Reelin through its canonical and non-canonical signaling in primary murine neurons during dendritic growth and arborization. We observed pathway crosstalk related to regulation of cytoskeleton, neuron projection development, protein transport, and actin filament-based process. We also found enriched gene sets exclusively by the non-canonical Reelin pathway including protein translation, mRNA metabolic process and ribonucleoprotein complex biogenesis suggesting Reelin fine-tunes neuronal structure through distinct signaling pathways. A key discovery is the identification of aldolase A, a glycolytic enzyme and actin binding protein, as a novel effector of Reelin signaling. Reelin induced de novo translation and mobilization of aldolase A from the actin cytoskeleton. We demonstrated that aldolase A is necessary for Reelin-mediated dendrite growth and arborization in primary murine neurons and mouse brain cortical neurons. Interestingly, the function of aldolase A in dendrite development is independent of its known role in glycolysis. Altogether, our findings provide new insights into the Reelin-dependent signaling pathways and effector proteins that are crucial for actin remodeling and dendritic development. Significance: Reelin is an extracellular glycoprotein and exerts its function primarily by binding to the canonical lipoprotein receptors Apoer2 and Vldlr. Reelin is best known for its role in neuronal migration during prenatal brain development. Reelin also signals through a non-canonical pathway outside of Apoer2/Vldlr; however, these receptors and signal transduction pathways are less defined. Here, we examined Reelin's role during dendritic outgrowth in primary murine neurons and identified shared and distinct pathways activated by canonical and non-canonical Reelin signaling. We also found aldolase A as a novel effector of Reelin signaling, that functions independently of its known metabolic role, highlighting Reelin's influence on actin dynamics and neuronal structure and growth.
RESUMO
Objective: The objective of this formative study was to gather women's perspectives in the design and communication modalities of a health kiosk set within a Planned Parenthood setting to promote patient education about the Human papillomavirus (HPV) and to motivate uptake of the HPV vaccine. Methods: Twenty-four women aged 18-35 participated in in-depth one-on-one interviews at a Planned Parenthood health center, which were analyzed in code-associated categories using NVivo11 Pro. Results: Most women showed receptivity to using an on-site health kiosk, as well as QR codes linked to text messages, to receive HPV-related health information outside of the clinic setting and reminders. Participants provided suggestions for kiosk design and communication modalities. Conclusions: Among low-income women we interviewed at Planned Parenthood, increasing HPV vaccination rates necessitates engaging digital health tools which incorporate both the preferences and needs of vulnerable populations. Innovation: Designing a point-of-service health kiosk that 1) draws on user preferences early in the design phase, 2) integrates multiple communication technologies, and 3) disseminates culturally grounded HPV vaccination decisions narratives that are tailored to vaccination awareness level is a promising approach in reducing barriers to HPV vaccine education and vaccine uptake among low-income women at safety-net clinics.