Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 17, Pages 7265-7270Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0702044104
Keywords
synapses; Rho GTPase; actin cytoskeleton; NMDA receptor
Categories
Funding
- NICHD NIH HHS [P30 HD 18655, P30 HD018655] Funding Source: Medline
- NINDS NIH HHS [T32 NS007484, NS 045500, NS 07484, R01 NS045500] Funding Source: Medline
Ask authors/readers for more resources
Dendritic spines are small, actin-rich protrusions on the surface of dendrites that receive the majority of excitatory synaptic inputs in the brain. The formation and remodeling of spines, processes that underlie synaptic development and plasticity, are regulated in part by Eph receptor tyrosine kinases. However, the mechanism by which Ephs regulate actin cytoskeletal remodeling necessary for spine development is not fully understood. Here, we report that the Rac1 guanine nucleotide exchange factor Tiam1 interacts with the EphB2 receptor in a kinase-dependent manner. Activation of EphBs by their ephrinB ligands induces the tyrosine phosphorylation and recruitment of Tiam1 to EphB complexes containing NMDA-type glutamate receptors. Either knockdown of Tiam1 protein by RNAi or inhibition of Tiam1 function with a dominant-negative Tiam1 mutant blocks dendritic spine formation induced by ephrinB1 stimulation. Taken together, these findings suggest that EphBs regulate spine development in part by recruiting, phosphorylating, and activating Tiam1. Tiam1 can then promote Rac1-dependent actin cytoskeletal remodeling required for dendritic spine morphogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available