Maintenance of cell type-specific connectivity and circuit function requires Tao kinase

Abstract

Sensory circuits are typically established during early development, yet how circuit specificity and function are maintained during organismal growth has not been elucidated. To gain insight we quantitatively investigated synaptic growth and connectivity in the Drosophila nociceptive network during larval development. We show that connectivity between primary nociceptors and their downstream neurons scales with animal size. We further identified the conserved Ste20-like kinase Tao as a negative regulator of synaptic growth required for maintenance of circuit specificity and connectivity. Loss of Tao kinase resulted in exuberant postsynaptic specializations and aberrant connectivity during larval growth. Using functional imaging and behavioral analysis we show that loss of Tao-induced ectopic synapses with inappropriate partner neurons are functional and alter behavioral responses in a connection-specific manner.Our data show that fine-tuning of synaptic growth by Tao kinase is required for maintaining specificity and behavioral output of the neuronal network during animal growth.

Neurodevelopmental disorder–associated mutations in TAOK1 reveal its function as a plasma membrane remodeling kinase

“…It is notable that among the three mammalian TAO kinases, TAOK1 is the most evolutionarily similar to the fly dTao and C. elegans kin-18; therefore, it is likely that the fly and worm Tao kinases are also plasma membrane sculpting proteins, a possibility that needs future experimental investigation. For example, loss of Tao in flies induces ectopic synapses, resulting in miswired connections that alter behavioral responses ( 19 ). This fine-tuning of synaptic connection by Tao kinase during neuronal network development might depend on its ability to remodel the plasma membrane.…”

“…TAOK1 is phosphorylated by the Hippo pathway kinase MST3, which is important for dendritic spine formation (16). In Drosophila melanogaster, activity of homolog dTao is required for neuroblast proliferation and neuronal connectivity (17)(18)(19). Kin-18 is a homolog of Tao kinases in Caenorhabditis elegans that is important for development of embryonic polarity (20).…”

A neuropeptidergic circuit gates selective escape behavior of Drosophila larvae

“…Labeling of synapses between Dp7 and v'td2 neurons using Syb-GRASP 46 was performed as described. 113 Larval brains (UAS-spGFP1-10-Syb, LexAop-spGFP11;73B01-Gal4/Ilp7-LexA) were dissected in 5 mM dissection buffer (108 mM NaCl, 5 mM KCl, 4 mM NaHCO3, 1 mM NaH 2 PO 4 , 5 mM Trehalose, 10mM Sucrose, 5 mM HEPES, 8.2 mM MgCl2, 2 mM CaCl 2 , pH 7.4), washed 3 times/5 s alternating between dissection buffer containing 5 mM KCl and 70 mM KCl, respectively, followed by 10 minutes ll Current Biology 32, 1-15.e1-e8, January 10, 2022 e4…”

“…Sample sizes were chosen similar to previous publications and commonly used in the field. 14,15,30,48,113 For comparison of two groups, unpaired Student's t test with Welch's correction was used, or nonparametric Mann-Whitney U test in case of non-normal distribution of the data. For analysis of mechanonociceptive behavior, the c2 test was used.…”