Zhang Huaye, Macara Ian G
Center for Cell Signaling, Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908-0577, USA.
Nat Cell Biol. 2006 Mar;8(3):227-37. doi: 10.1038/ncb1368. Epub 2006 Feb 12.
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.
PAR-3（分区缺陷基因3）在包括轴突特化在内的许多情况下对细胞极化至关重要。然而，极性蛋白尚未被认为参与神经元分化的后期步骤，如树突棘形态发生。在这里，我们表明PAR-3对原代海马神经元的正常棘突发育是必需的。PAR-3的缺失导致形成多个丝状伪足和片状伪足样树突突起——一种类似于表达活化Rac的神经元的表型。PAR-3通过结合Rac鸟嘌呤核苷酸交换因子（GEF）TIAM1来调节棘突形成，并将其空间限制在树突棘上。因此，PAR-3和TIAM1的平衡对于调节Rac-GTP水平和允许棘突形态发生至关重要。
