RRC ID 21840
著者 Stephan D, Sánchez-Soriano N, Loschek LF, Gerhards R, Gutmann S, Storchova Z, Prokop A, Kadow IC.
タイトル Drosophila Psidin regulates olfactory neuron number and axon targeting through two distinct molecular mechanisms.
ジャーナル J Neurosci
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.
巻・号 32(46)
ページ 16080-94
公開日 2012-11-14
DOI 10.1523/JNEUROSCI.3116-12.2012
PII 32/46/16080
PMID 23152593
PMC PMC6794014
MeSH Acetyltransferases / metabolism Animals Axons / physiology* Blood Proteins / physiology* Blotting, Western Cell Count Cells, Cultured Drosophila / physiology* Drosophila Proteins / physiology* Genotype Growth Cones / physiology Immunoprecipitation In Situ Hybridization Nerve Net / cytology Nerve Net / growth & development Nerve Net / physiology Neurons / physiology* Olfactory Pathways / cytology Olfactory Pathways / growth & development Olfactory Pathways / physiology* Phenotype Phosphorylation / physiology Pseudopodia / physiology RNA Interference Saccharomyces cerevisiae / metabolism Tropomyosin / pharmacology
IF 5.674
引用数 7
WOS 分野 NEUROSCIENCES
リソース情報
ショウジョウバエ 14222R-3 14222R-4