title: Drosophila Psidin regulates olfactory neuron number and axon targeting through two distinct molecular mechanisms.
abstract: 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, is suppressed by parallel removal of Tropomyosin. In contrast, Psidin functions as the noncatalytic subunit of the N-acetyltransferase complex B (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. 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.
authors.affiliation: Sensory Neurogenetics Research Group, Max Planck Institute of Neurobiology, 82152 Martinsried, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Stephan
authors.forename: Natalia
authors.initials: N
authors.lastname: Sánchez-Soriano
authors.forename: Laura F
authors.initials: LF
authors.lastname: Loschek
authors.forename: Ramona
authors.initials: R
authors.lastname: Gerhards
authors.forename: Susanne
authors.initials: S
authors.lastname: Gutmann
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Storchova
authors.forename: Andreas
authors.initials: A
authors.lastname: Prokop
authors.forename: Ilona C Grunwald
authors.initials: IC
authors.lastname: Kadow
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000502:physiology*; D001798:Blood Proteins / Q000502:physiology*; D015153:Blotting, Western; D002452:Cell Count; D002478:Cells, Cultured; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology*; D005838:Genotype; D020439:Growth Cones / Q000502:physiology; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D009415:Nerve Net / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009833:Olfactory Pathways / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D010641:Phenotype; D010766:Phosphorylation / Q000502:physiology; D011554:Pseudopodia / Q000502:physiology; D034622:RNA Interference; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D014335:Tropomyosin / Q000494:pharmacology
chemical_list: D001798:Blood Proteins; D029721:Drosophila Proteins; D014335:Tropomyosin; C518075:psidin protein, Drosophila; D000123:Acetyltransferases