Acknowledgments Firstly, I would like to express my sincere gratitude to my supervisor Prof. dr. Martina Schmidt for the continuous support of my Ph. D study and related research, especially for your patience with my non-orthodox ways of work. Your guidance helped me throughout the course of research and writing this thesis. Thank you for allowing me to work under your command within the University of Groningen. I will always be grateful. Secondly, I would like to thank Prof. dr. Erik Boddeke for your insightful comments and encouragement. You provided me the opportunity to join your team and have access to the laboratory and research facilities. Without your support it would not be possible to conduct all this research. A very special thanks to Prof. dr. Christian González, because thanks to your motivation and encouragement during all these years I could fight against all the obstacles and problems inside and outside the lab. Working in your lab made a difference in my career. It was under your tutelage that I developed my skills as a scientist. You provided me with direction, technical support and friendship in an environment that made it possible to finish my work in Chile and in The Netherlands. I owe you my eternal gratitude. Thanks to all the professors of the PhD in Sciences, mention in Molecular and Cellular Biology and Neurosciences from Universidad de Chile. Finally, thanks to Dr. Alejandra Alvarez from Pontificia Universidad Católica de Chile and Dr. Alexies Dagnino from Universidad de Valparaiso for being part of my undergrad education. 376 RUG I would like to thank the whole group of the Department of Molecular Pharmacology. Thanks for the continuous support since 2011 when I first joined the group in Groningen. Prof. dr Herman Meurs, thank you for your warm welcome at the beginning and every time that I returned to Groningen and your support in the laboratory. Prof dr. Reinoud Gosens, thanks for all the honest conversations, scientific advice and your company in social events. Carolina and Mark thank you for all your support in the lab, your smile every morning and support with every lab-related issue. I really appreciated your help. Wilfred, I owe you my gratitude for being there when I started, helping me with any issues concerning living in this country as well as working in the laboratory. You were a great help to me. Thanks for helping me understand the Dutch way of living and to be more confident as a scientist. You are a true friend, although I still do not understand your Frisian way. I hope we can always be in contact. Tim, from the beginning we had a connection as friends and quickly became brothers during these years. Thanks for your help and friendship, especially during my last year in Groningen. I will always remember all our trips and conversations about life and science. And as we always say, “this is a brotherhood that will last forever”. David, thanks for your honest friendship and all your help. We were together in the lab for a short period but became brothers together with Tim. I will 377 always have good memories of our trips, jokes, and conversations about life and the British ways. I am very happy to have you as a friend. Tjitske, thanks for being the sister that I never had, for all the daily dirty jokes and your female support when I needed it. I have a lot of respect for you as person and scientist. Bing, my friend, I admire you for your continuous struggle against all the obstacles that you face, while still sharing a smile and brining positive energy. Thanks for sharing your amazing food with me and teaching me about the Chinese culture. Thanks for your friendship and help. Vessa, thanks for being an awesome roommate and always having food for Tim and me (cookies!). I am very glad that I know you and am also happy that you will be the eternal companion of my friend Wilfred. Keep fighting and smiling and never surrender. Haoxiao, thanks for being a good roommate and dealing with all our jokes. I wish you all the success in your projects and life with Bing. Anouk, thanks for all your help and patience with the animals. Without you it would be very difficult to perform the experiments. Thanks to my students, Janke, Chris, and Kevin for all your patience, help and hard work during my research. Thanks to the rest of the colleagues from the lab: Hana, Sepp, Kuldeep, Eline, Hoeke, Bart, Marieke, Jacques, Sophie, Loes, and Anita. 378 UMCG Department of medical physiology Thanks to Michel Meijer for helping me with all my experiments, requirements, and problem solving during my research all these year. Thanks to Trix van der Sluiz-Rozema for being an amazing secretary, always helping me with my doubts about the project and support me with my requirements for my research. Thanks to Marcin Czepiel and Ilia Vainchtein for the support in the laboratory during my experiments. Special thanks to all the people from the CDP, GUIDE, GSSM, BCN that were involved in this project. Thanks to your work I could do my research in the Netherlands and in the University of Groningen. Microscopy Center Dear Klaas Sjollema thanks for your precious help with my experiments in the microscopy center and for your patience, help and knowledge. Thanks to you I have always felt very comfortable to work in the imaging center. Universidad de Chile Gracias a todos mis compañeros en el laboratorio CENEDYN y del doctorado, en especial a Cristina Olmos por siempre ser una gran amiga y apoyo durante todos estos años en el doctorado. Dentro y fuera del laboratorio fuiste un pilar, sin ti no podría haber logrado avanzar en mi tesis, por eso te estaré siempre agradecido. A David Villarroel por su paciencia, amistad, ayuda y compartir nuestra vida diaria además de los experimentos. Felipe Bodaleo por su amistad y ayuda 379 durante nuestro tiempo en el laboratorio y todos los buenos momentos vividos después de la jornada laboral. Muchas gracias a Daniel Henriquez Y Carlos Wilson por su gran trabajo y ayuda en nuestro paper en el JNS. Gracias Erik Contreras, Daniel Borquez y Carolina Montenegro por su gran ayuda durante mis inicios en el laboratorio y por siempre estar presentes cuando lo necesitaba. Familia Este trabajo está dedicado a mi madre Lijia LLancao por su gran amor y apoyo durante toda mi vida estudiando, sin ella nada de esto sería posible. En honor a ella dedico todos los papers que puedan salir de este trabajo. Mi futuro como professional y persona sera para honrar siempre su apellido. Gracias por ser la gran madre que eres. A mi hermano Eduardo Aburto LLancao por su amor infinito y paciencia conmigo durante todos estos años de estudios que sin duda nos pusieron a prueba pero ahora que ya hemos terminado solo quiero dedicarte este trabajo por ser un gran amigo y hermano. Gracias Andrea por ser una gran cuñada y una super mama de Lucas, tener a mi sobrino ha sido una de las grandes alegrias de mi vida. Gracias a mi familia LLancao; tios Josue, Eric, Pascual, Ivan, Juan, Juanito, Salomon y Elias. Por sus cuidados durante mi infancia y siempre estar presentes para mi madre. A mi abuela Lucrecia le dedico esta tesis por todos tus cuidados y amor Para con mi hermano y conmigo, honraré tu nombre siempre. 380