The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesis.
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.
Zhang
Huaye
H
Center for Cell Signaling, Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908-0577, USA. hz5a@virginia.edu
Macara
Ian G
IG
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D016764:Cell Polarity; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D004622:Embryo, Mammalian / Q000166:cytology; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D009024:Morphogenesis; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins; D011554:Pseudopodia / Q000648:ultrastructure; D051381:Rats; D016704:Synapsins / Q000378:metabolism; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C472451:Pard3 protein, rat; D016704:Synapsins; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C513259:Tiam1 protein, rat; D020744:rac GTP-Binding Proteins