Ultanir SK, et al. (2012) Chemical Genetic Identification of NDR1/2 Kinase Substrates AAK1 and Rabin8 Uncovers Their Roles in Dendrite Arborization and Spine Development. Neuron 73(6):1127-42
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.CI - Copyright (c) 2012 Elsevier Inc. All rights reserved.
|Status: Published||Type: Journal Article||PubMed ID: 22445341|
Topics addressed in this paper
Number of different genes curated to this paper: 3
- To find other papers on a gene and topic, click on the colored ball in the appropriate box.
- displays other papers with information about that topic for that gene.
- displays other papers in SGD that are associated with that topic.
The topic is addressed in these papers but does not describe a specific gene or chromosomal feature.
- To go to the Locus page for a gene, click on the gene name.