Both the phosphoinositide and receptor binding activities of Dab1 are required for Reelin-stimulated Dab1 tyrosine phosphorylation

Authors:
Xu M, Arnaud L, Cooper JA
In:
Source: Brain Res Mol Brain Res
Publication Date: (2005)
Issue: 139(2): 300-5
Research Area:
Neurobiology
Cells used in publication:
Neuron, cortical, mouse
Species: mouse
Tissue Origin: brain
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
Reelin-stimulated tyrosine phosphorylation of the Dab1 adaptor protein is required during brain development for Reelin-dependent neuron positioning in the cerebral cortex and various other laminated regions. Dab1 contains an amino-terminal PTB/PI domain through which it can bind to Reelin receptors and membrane phosphoinositides. The relative contributions of these binding activities were unknown. Here, we identify a mutation in the PTB domain of Dab1 that inhibits membrane localization without inhibiting receptor binding. In neurons, this mutation reduces both basal and Reelin-stimulated Dab1 tyrosine phosphorylation. In contrast, a mutation that inhibits receptor binding reduces Reelin-stimulated but not basal tyrosine phosphorylation. These results support a model in which phospholipids recruit Dab1 to membranes but do not play a direct role in relaying the Reelin signal, while direct Dab1-receptor interaction is responsible for relaying the Reelin signal but not for membrane recruitment.