It has long been established that neuronal growth cone navigation depends on changes in microtubule (MT) and F-actin architecture downstream of guidance cues. However, the mechanisms by which MTs and F-actin are dually coordinated remain a fundamentally unresolved question. Here, we report that the well-characterized MT polymerase, XMAP215 (also known as CKAP5), plays an important role in mediating MT-F-actin interaction within the growth cone. We demonstrate that XMAP215 regulates MT-F-actin alignment through its N-terminal TOG 1-5 domains. Additionally, we show that XMAP215 directly binds to F-actin in vitro and co-localizes with F-actin in the growth cone periphery. We also find that XMAP215 is required for regulation of growth cone morphology and response to the guidance cue, Ephrin A5. Our findings provide the first strong evidence that XMAP215 coordinates MT and F-actin interaction in vivo. We suggest a model in which XMAP215 regulates MT extension along F-actin bundles into the growth cone periphery and that these interactions may be important to control cytoskeletal dynamics downstream of guidance cues. This article has an associated First Person interview with the first author of the paper.
Background/Purpose: To identify geographic and socioeconomic variables predictive of residential proximity to retinopathy of prematurity (ROP) clinical trial locations.Methods: This cross-sectional epidemiological study used census tract-level data from three national public data sets and trial-level data from ClinicalTrials.gov. Socioeconomic predictors of driving distance and time to the nearest ROP clinical trial location were identified. Primary outcomes were time .60 minutes and distance .60 miles traveled to the nearest ROP clinical trial site.Results: Multivariate analysis showed that residents were more likely to travel .60 minutes to the nearest ROP clinical trial site if they lived in census tracts that were rural (adjusted odds ratio 1.20, P = 0.0002), had higher percentages of the population living # federal poverty level (fourth quartile vs. first quartile, adjusted odds ratio 1.19, P , 0.0001), or had less education (associate vs. bachelor's degree, adjusted odds ratio 1.01, P ,0.007). By contrast, counties with higher percentages of births with birth weight ,1500 g (adjusted odds ratio 0.88, P = 0.0062) were less likely to travel .60 minutes. Similar variables predicted travel distance.Conclusion: Although counties with higher incidences of very low-birth-weight infants were closer to ROP clinical trial sites, residents living in rural and low-income census tracts had significantly greater travel burdens.
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