Regulation of Spine Density and Morphology by IQGAP1 Protein Domains

IQGAP1 is a scaffolding protein that regulates spine number. We now show a differential role for IQGAP1 domains in spine morphogenesis, in which a region of the N-terminus that promotes Arp2/3-mediated actin polymerization and branching stimulates spine head formation while a region that binds to Cdc42 and Rac is required for stalk extension. Conversely, IQGAP1 rescues spine deficiency induced by expression of dominant negative Cdc42 by stimulating formation of stubby spines. Together, our observations place IQGAP1 as a crucial regulator of spine number and shape acting through the N-Wasp Arp2/3 complex, as well as upstream and downstream of Cdc42.

IQGAP1是一种调控树突棘数量的支架蛋白。本研究揭示了IQGAP1各结构域在树突棘形态发生中的差异化功能：其N端一段可介导Arp2/3复合物依赖的肌动蛋白聚合与分支的区域，能够促进树突棘头的形成；而一段结合Cdc42与Rac的区域，则是棘柄延伸所必需的。反之，IQGAP1可通过刺激短粗型树突棘的形成，挽救显性负性Cdc42过表达诱导的树突棘缺陷。综上，本研究结果证实，IQGAP1通过N-Wasp-Arp2/3复合物，并作为Cdc42的上游及下游调控因子，在树突棘的数量与形态调控中发挥关键作用。