The acquisition and maintenance of spatial differences in structure of the neuron, a phenomenon referred to as neuronal polarity, is a crucial event that may be key in understanding neuronal wiring fundamental to our brain function. The aim of this thesis was to investigate how EPAC, a protein activated by the second messenger cyclic AMP (cAMP), controls neuronal polarity, using freshly isolated hippocampal neurons from mouse brain. We observed that pharmacological inhibition of EPAC and genetic activation can induce opposite changes in terms of neuronal morphology. Inhibition creates neurons with multiple axons, whereas activation reduces the length of the axon and the number of neurons that are polarized, a phenomenon shared by several other regulators of polarity. Mechanistically, we determined that an important target of EPAC in the regulation of neuronal polarity is Rap1B, a small GTPase that historically has also been observed to drive polarization processes. The solidity of this signalling event becomes evident by the fact that also in neuroblastoma cells EPAC activation can lead to the development of axon-like structures, a phenomenon that was previously only attributed to PKA, which is also activated by cAMP. The work presented here provides a better understanding of the mechanisms underlying neuronal polarity and the development of the axon, expanding on the functions of cyclic AMP in this system and highlighting EPAC as a crucial and novel mediator of cAMP-driven polarity.
Every two weeks, UG Makers puts the spotlight on a researcher who has created something tangible, ranging from homemade measuring equipment for academic research to small or larger products that can change our daily lives. That is how UG...
As a part of the Jantina Tammes School, the 'Language and AI' theme is an interdisciplinary initiative that aims to encourage collaboration among academics, PhD candidates, students, and industry representatives who share a keen interest in the...
Prof. Moniek Tromp has been appointed Captain of Science of the Chemistry Top Sector by the Minister of Economic Affairs and Climate Policy. As from 1 July 2023, she succeeded Prof. Bert Weckhuysen from Utrecht University.
The UG website uses functional and anonymous analytics cookies. Please answer the question of whether you want to accept
or reject other cookies (such as tracking cookies).
If no choice is made, only basic cookies will be stored. More information