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.
Last week, Ben Feringa and Anouk Lubbe presented the first copy of their book Alledaagse Moleculen (Everyday Molecules) to minister Robbert Dijkgraaf. The richly illustrated book offers an accessible overview of 180 substances in our daily lives....
Dr Annette Scheepstra of the UG Arctic Centre, part of the Faculty of Arts, is about to conduct research into tourism in Antarctica and how tourists can become Antarctic ambassadors. She has been granted €1 million in funding by the Dutch Research...
The Royal Netherlands Academy of Arts and Sciences (KNAW) has appointed Professor Maria Loi and Professor Dirk Slotboom from the Faculty of Science and Engineering as members of the Academy.
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