FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

Receptor Sorting within Endosomal Trafficking Pathway Is Facilitated by Dynamic Actin Filaments

Early endosomes (EEs) are known to be a sorting station for internalized molecules destined for degradation, recycling, or other intracellular organelles. Segregation is an essential step in such sorting, but the molecular mechanism of this process remains to be elucidated. Here, we show that actin is required for efficient recycling and endosomal maturation by producing a motile force. Perturbation of actin dynamics by drugs induced a few enlarged EEs containing several degradative vacuoles and also interfered with their transporting ability. Actin repolymerization induced by washout of the drug caused the vacuoles to dissociate and individually translocate toward the perinuclear region. We further elucidated that cortactin, an actin-nucleating factor, was required for transporting contents from within EEs. Actin filaments regulated by cortactin may provide a motile force for efficient sorting within early endosomes. These data suggest that actin filaments coordinate with microtubules to mediate segregation in EEs

Risk of female athlete triad development in Japanese collegiate athletes is related to sport type and competitive level

Akemi Sawai,1,* Bryan J Mathis,2,* Hiroaki Natsui,3 Alexander Zaboronok,2 Risa Mitsuhashi,1 Yuki Warashina,4 Noboru Mesaki,4 Hitoshi Shiraki,4 Koichi Watanabe4 1Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan; 2Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; 3Faculty of Sports and Health Sciences, Japan Women’s College of Physical Education, Setagaya-ku, Tokyo, Japan; 4Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan *These authors contributed equally to this work Introduction: Menstrual dysfunction, musculoskeletal injury, and poor nutrition combine to form the female athlete triad (FAT), which results in serious health consequences for affected athletes. To this point, the risk factors of this phenomenon have not been fully explored in Japanese female college athletes. Additionally, the effect of competitive level on FAT risk factors has also not been reported. Therefore, we aimed to examine FAT risk factors in Japanese female athletes of various sports as well as examine the impact of competitive level on FAT.Methods: A Japanese-language survey was completed by 531 athletes and 20 nonathletes at two Japanese universities and answers with regard to menstrual status, musculoskeletal injury, nutrition, and other variables were analyzed based on classification of the sports into nine distinct groups based on activity type. Sport intensity, training volume, and competitive levels were used to further classify each sport. One-way ANOVA and the Bonferroni post hoc test using SPSS were carried out to analyze significance for relationships between sport intensity and FAT risk factors. Additionally, the relationship between competitive level and FAT risk factors was analyzed by ANOVA and Bonferroni post hoc tests.Results: Sport intensity was positively correlated with a delay in menarche as well as dysmenorrhea and poor nutrition while musculoskeletal injury was correlated with repetitive, high-training volume sports. Lower competitive levels increased dysmenorrhea but did not impact injury status or nutrition.Conclusion: Sport intensity and training volume, but not competitive level, are the critical factors affecting FAT risk in Japanese female college athletes. Keywords: athletes, dysmenorrhea, FAT, female, Japanese, tria

Confirmation of delayed menarche based on regression evaluation of age at menarche for age at MPV of height in female ball game players

A general delay in menarche in female athletes has been confirmed based on comparisons of mean ages between athletes and non-athletes; however, it has not been possible to judge such delays individually. If delayed menarche could be evaluated for an individual, the athlete could be advised as to necessary precautions. In this study, the age at maximum peak velocity (MPV) of height, adopted as an index of physical maturation, was identified by the wavelet interpolation method (WIM). The relationship between the age at menarche and age at MPV of height in female athletes and non-athletes was then examined. For the athlete group, health examination records of 90 female ball game players in the first year of university in the Tokai area, all of whom had participated in national level competitions, were reviewed for the period from the first grade of elementary school until the final year of high school (from 1985 to 1996). A similar examination was conducted for the control group, among whom a final group of 78 female non-athletes were selected. The age at menarche was determined by questionnaires, and the longitudinal data for height and weight were obtained from the health examination records. Based on a comparison of the difference between the age at MPV of height and age at menarche in ball game players and the control group, a tendency was seen for the difference between the two ages to narrow as the age at MPV of height rose. A corrected regression evaluation of age at menarche against age at MPV of height was derived in the control group, and the evaluation system was applied to ball game players. The delay in menarche in ball game players could be individually evaluated