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Drosophila Psidin regulates olfactory neuron number and axon targeting through two distinct molecular mechanisms

Stephan, D., Sánchez-Soriano, N., Loschek, L.F., Gerhards, R., Gutmann, S., Storchova, Z., Prokop, A., Grunwald Kadow, I.C

J. Neurosci. 2012;32(46):16080-16094.

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The formation of neuronal circuits is a key process of development, laying foundations for behavior. The cellular mechanisms regulating circuit development are not fully understood. Here, we reveal Psidin as an intracellular regulator of Drosophila olfactory system formation. We show that Psidin is required in several classes of olfactory receptor neurons (ORNs) for survival and subsequently for axon guidance. During axon guidance, Psidin functions as an actin regulator and antagonist of Tropomyosin. Accordingly, Psidin-deficient primary neurons in culture display growth cones with significantly smaller lamellipodia. This lamellipodial phenotype as well as the mistargeting defects in vivo are suppressed by parallel removal of Tropomyosin. In contrast, Psidin functions as the non-catalytic subunit of the N-acetyltransferase complex NatB to maintain the number of ORNs. Psidin physically binds the catalytic NatB subunit CG14222 (dNAA20) and functionally interacts with it in vivo. We define the dNAA20 interaction domain within Psidin and identify a conserved serine as a candidate for phosphorylation-mediated regulation of NatB complex formation. A phosphomimetic mutation of this serine showed severely reduced binding to dNAA20 in vitro. In vivo, it fully rescued the targeting defect, but not the reduction in neuron numbers. In addition, we show that a different amino acid point mutation shows exactly the opposite effect by rescuing only the cell number but not the axon targeting defect. Taken together, our data suggest that Psidin plays two independent developmental roles via the acquisition of separate signaling pathways both of which contribute to the formation of olfactory circuits. [PubMed:]

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Created by:
Prokop, Andreas
7th September, 2012, 05:36:20
Last modified by:
Prokop, Andreas
Last modified:
20th November, 2012, 13:24:48

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