Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Dendritic Spines / metabolism*
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Female
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Gene Expression
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Hippocampus / cytology
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Mutation
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Neurons / cytology*
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Neurons / metabolism*
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Pregnancy
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Protein Interaction Domains and Motifs*
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Rats
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Receptors, N-Methyl-D-Aspartate / metabolism
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ras GTPase-Activating Proteins / chemistry
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ras GTPase-Activating Proteins / genetics
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ras GTPase-Activating Proteins / metabolism*
Substances
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IQ motif containing GTPase activating protein 1
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Receptors, N-Methyl-D-Aspartate
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ras GTPase-Activating Proteins
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N-methyl D-aspartate receptor subtype 2A
Grants and funding
This work was supported by grants from MINCyT, CONICET and Agencia Cordoba Ciencia to AC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.