Nature Cell Biology 8, 227 - 237 (2006)
Published online: 12 February 2006; | doi:10.1038/ncb1368
The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesisHuaye Zhang
& Ian G. Macara
Center for Cell Signaling, Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908-0577, USA.
Correspondence should be addressed to Huaye Zhang hz5a@virginia.edu
PAR-3 (partitioning-defective gene 3) is essential for cell polarization in many contexts, including axon specification. However, polarity proteins have not been implicated in later steps of neuronal differentiation, such as dendritic spine morphogenesis. Here, we show that PAR-3 is necessary for normal spine development in primary hippocampal neurons. Depletion of PAR-3 causes the formation of multiple filopodia- and lamellipodia-like dendritic protrusions — a phenotype similar to neurons expressing activated Rac. PAR-3 regulates spine formation by binding the Rac guanine nucleotide-exchange factor (GEF) TIAM1, and spatially restricting it to dendritic spines. Thus, a balance of PAR-3 and TIAM1 is essential to modulate Rac–GTP levels and to allow spine morphogenesis.
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