Reelin controls neuronal positioning in the developing brain by binding to the two lipoprotein receptors, very-low-density lipoprotein receptor and apolipoprotein E receptor 2, to stimulate phosphorylation of Disabled-1 (Dab1) by the Fyn and Src tyrosine kinases. Crk and Crk-like (CrkL) have been proposed to interact with tyrosine phosphorylated Dab1 to… (More)
Neurons of the developing brain are especially vulnerable to environmental agents that damage DNA (i.e., genotoxicants), but the mechanism is poorly understood. The focus of the present study is to demonstrate that DNA damage plays a key role in disrupting neurodevelopment. To examine this hypothesis, we compared the cytotoxic and DNA damaging properties of… (More)
Agrin, released by motor neurons, promotes neuromuscular synapse formation by stimulating MuSK, a receptor tyrosine kinase expressed in skeletal muscle. Phosphorylated MuSK recruits docking protein-7 (Dok-7), an adaptor protein that is expressed selectively in muscle. In the absence of Dok-7, neuromuscular synapses fail to form, and mutations that impair… (More)
We previously reported that the aqueous extract from a medicinal plant Dryobalanops aromatica specifically inhibits the nicotinic acetylcholine receptor (nAChR) (Oh et al. Pharmacol Res 2000;42(6):559-64). Here, the effect of borneol, the main constituent of D. aromatica, on nAChR activity was investigated in bovine adrenal chromaffin cells. Borneol… (More)
The genotoxicant methylazoxymethanol (MAM) is a widely used developmental neurotoxin, and its glucoside is an etiological factor for western Pacific amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS/PDC). Identification of global protein expression changes that occur in response to MAM in the developing cerebellum could provide valuable… (More)
Excessive demands on the protein folding capacity of the endoplasmic reticulum (ER) cause irremediable ER stress and contribute to cell loss in a number of cell degenerative diseases, including type 2 diabetes and neurodegeneration 1,2. The signals communicating catastrophic ER damage to the mitochondrial apoptotic machinery remain poorly understood 3-6. We… (More)
Activation of the slit diaphragm protein nephrin induces actin cytoskeletal remodeling, resulting in lamellipodia formation in podocytes in vitro in a phosphatidylinositol-3 kinase-, focal adhesion kinase-, Cas-, and Crk1/2-dependent fashion. In mice, podocyte-specific deletion of Crk1/2 prevents or attenuates foot process effacement in two models of… (More)
The dendritic planarity of Purkinje cells is critical for cerebellar circuit formation. In the absence of Crk and CrkL, the Reelin pathway does not function resulting in partial Purkinje cell migration and defective dendritogenesis. However, the relationships among Purkinje cell migration, dendritic development and Reelin signaling have not been clearly… (More)
Reelin choreographs neuronal migration to establish laminar structures during brain formation. A recent paper uncovers a new function for Reelin signaling in specifying dendritic compartmentalization. Reelin-induced tyrosine phosphorylation is responsible for enrichment of ion channels in dendritic tufts.
Disabled-1 is a key signaling molecule in the Reelin pathway that plays a critical role in neuronal migration and positioning during brain development. In this issue of Neuron, Yano et al. demonstrate that the neuron-specific RNA binding protein Nova2 contributes to neuronal migration by regulating alternative splicing of disabled-1.