Abstract
Rac1 and Cdc42, members of the Rho family GTPases, control diverse cellular processes such as cell migration and morphogenesis through their effectors. Among the effectors, IQGAP1 plays pivotal roles in the establishment of cytoskeletal architecture and intercellular adhesions in various cells. However, its roles remain to be clarified, especially in neuronal cells. We have identified IQGAP3 as a novel member of the IQGAP family, which is highly expressed in brain. We found that IQGAP3, an effector of Rac1 and Cdc42, associates directly with actin filaments and accumulates asymmetrically at the distal region of axons in hippocampal neurons. The depletion of IQGAP3 impairs neurite or axon outgrowth in neuronal cells with the disorganized cytoskeleton, but depletion of IQGAP1 does not. Furthermore, IQGAP3 is indispensable for Rac1/Cdc42-promoted neurite outgrowth in PC12 cells. Taken together, these results indicate that IQGAP3 can link the activation of Rac1 and Cdc42 with the cytoskeletal architectures during neuronal morphogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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COS Cells
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Chlorocebus aethiops
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Cytoskeleton / metabolism
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Fluorescent Antibody Technique, Direct
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GTPase-Activating Proteins / chemistry
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GTPase-Activating Proteins / genetics
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GTPase-Activating Proteins / metabolism*
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Glutathione Transferase / metabolism
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Green Fluorescent Proteins / metabolism
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Molecular Sequence Data
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Neurites / physiology*
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PC12 Cells
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Protein Structure, Tertiary
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RNA Interference
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RNA, Small Interfering / metabolism
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Rats
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Recombinant Fusion Proteins / metabolism
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Sequence Homology, Amino Acid
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cdc42 GTP-Binding Protein / metabolism*
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rac1 GTP-Binding Protein / 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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Actins
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GTPase-Activating Proteins
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IQGAP3 protein, rat
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RNA, Small Interfering
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Recombinant Fusion Proteins
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ras GTPase-Activating Proteins
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Green Fluorescent Proteins
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Glutathione Transferase
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cdc42 GTP-Binding Protein
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rac1 GTP-Binding Protein