{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ultanir SK"],"funding":["NIBIB NIH HHS","Howard Hughes Medical Institute","NCRR NIH HHS","NIMH NIH HHS","NINDS NIH HHS","NIGMS NIH HHS"],"pagination":["1127-42"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3333840"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["73(6)"],"pubmed_abstract":["Dendrite arborization and synapse formation are essential for wiring the neural circuitry. The evolutionarily conserved NDR1/2 kinase pathway, important for polarized growth from yeast to mammals, controls dendrite growth and morphology in the worm and fly. The function of NDR1/2 in mammalian neurons and their downstream effectors were not known. Here we show that the expression of dominant negative (kinase-dead) NDR1/2 mutants or siRNA increase dendrite length and proximal branching of mammalian pyramidal neurons in cultures and in vivo, whereas the expression of constitutively active NDR1/2 has the opposite effect. Moreover, NDR1/2 contributes to dendritic spine development and excitatory synaptic function. We further employed chemical genetics and identified NDR1/2 substrates in the brain, including two proteins involved in intracellular vesicle trafficking: AAK1 (AP-2 associated kinase) and Rabin8, a GDP/GTP exchange factor (GEF) of Rab8 GTPase. We finally show that AAK1 contributes to dendrite growth regulation, and Rabin8 regulates spine development."],"journal":["Neuron"],"pubmed_title":["Chemical genetic identification of NDR1/2 kinase substrates AAK1 and Rabin8 Uncovers their roles in dendrite arborization and spine development."],"pmcid":["PMC3333840"],"funding_grant_id":["R01 MH077694","R01 EB001987","R01EB001987","R01 MH084234-08","R37 NS040929","RR001614","P41 RR001614","P41 GM103481","S10 RR015804","5R01MH084234","R01 MH084234","RR015804","R37NS040929","R01 MH066084"],"pubmed_authors":["Li G","Ultanir SK","Burlingame AL","Hertz NT","Jan LY","Pleasure SJ","Ge WP","Shokat KM","Jan YN"],"additional_accession":[]},"is_claimable":false,"name":"Chemical genetic identification of NDR1/2 kinase substrates AAK1 and Rabin8 Uncovers their roles in dendrite arborization and spine development.","description":"Dendrite arborization and synapse formation are essential for wiring the neural circuitry. The evolutionarily conserved NDR1/2 kinase pathway, important for polarized growth from yeast to mammals, controls dendrite growth and morphology in the worm and fly. The function of NDR1/2 in mammalian neurons and their downstream effectors were not known. Here we show that the expression of dominant negative (kinase-dead) NDR1/2 mutants or siRNA increase dendrite length and proximal branching of mammalian pyramidal neurons in cultures and in vivo, whereas the expression of constitutively active NDR1/2 has the opposite effect. Moreover, NDR1/2 contributes to dendritic spine development and excitatory synaptic function. We further employed chemical genetics and identified NDR1/2 substrates in the brain, including two proteins involved in intracellular vesicle trafficking: AAK1 (AP-2 associated kinase) and Rabin8, a GDP/GTP exchange factor (GEF) of Rab8 GTPase. We finally show that AAK1 contributes to dendrite growth regulation, and Rabin8 regulates spine development.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Mar","modification":"2020-10-29T12:02:19Z","creation":"2019-03-27T00:52:34Z"},"accession":"S-EPMC3333840","cross_references":{"pubmed":["22445341"],"doi":["10.1016/j.neuron.2012.01.019"]}}