The Janus face of Psidin – One protein in two pathways

The formation of neuronal networks relies on the proper development and targeting of the neurons within. The actin cytoskeleton plays an important role during the process of axon guidance. The non-catalytic subunit of the Drosophila NatB complex, Psidin, is essential to maintain the actin cytoskeleton in a dynamic and responsive state. At the same time Psidin, together with the catalytic part of the NatB complex, is required for the survival of neurons.

HFSP Career Development Award holder Ilona Grunwald-Kadow and colleagues
authored on Thu, 22 November 2012

Once a neuron forms an axon, it starts growing towards a certain ‘target zone’.  In that zone it will eventually form a synapse with a partner neuron.  The large number of underlying axon targeting mechanisms is controlled by an even larger number of extracellular cues provided by the surrounding environment. Symbolizing the forefront of an axon, the growth cone is the part of the neuron that comes into contact with such cues and is responsible for integrating them. However, it remains mostly elusive how these attractive or repellent cues affect neurons at subcellular levels.

We investigated the role of the highly conserved actin binding protein, Psidin, during the development and targeting of olfactory receptor neurons in Drosophila.  Furthermore, we were able to demonstrate that Psidin uses two independent molecular mechanisms to control neuron targeting and survival. Our results show that Psidin is required at two different time points during the development of the olfactory system.

During early neuronal development, Psidin is required as a non-catalytic part of the N-acetyltransferase complex (NatB) to ensure neuronal survival.  During this stage Psidin interacts with the catalytic subunit of the NatB-complex (dNAA20).  We were able to characterize the formation of the NatB-complex showing that selective phosphorylation of a conserved serine residue in Psidin is used for its regulation. In addition, we successfully mapped a minimal interaction domain between the two proteins.

Later during axon targeting, Psidin acts as an actin binding protein to regulate actin dynamics in the growth cone. The loss of Psidin leads to significantly reduced lamellipodia. We showed that Psidin interacts with other actin modulating proteins (e.g. Cofilin, LimK).  In neurons, Psidin maintains the lamellipodia size and keeps the cytoskeleton in a dynamic and responsive state. This ensures that the growth cones and ultimately the growing axon can respond properly to various guidance cues.

Due to Psidin’s strong conservation in higher organisms, we hope that our findings provide important insights into the function of Psidin’s mammalian homologues and that our characterization could support research aimed at understanding regeneration and degeneration of the nervous system.

  

Reference

Drosophila Psidin regulates olfactory neuron number and axon targeting through two distinct molecular mechanisms.  Daniel Stephan, Natalia Sánchez-Soriano, Laura F. Loschek, Ramona Gerhards, Susanne Gutmann, Zuzana Storchova, Andreas Prokop and Ilona C. Grunwald Kadow.  The Journal of Neuroscience, 14 November 2012, 32(46):16080-16094;doi:10.1523/JNEUROSCI.3116-12.2012.