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IQGAP2 and Neurite Outgrowth: AKAP220 Tying the Knots
Author(s) -
Müllendorff Karin Andrea,
Tunquist Brian,
Scott John D.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.822.4
Subject(s) - neurite , microbiology and biotechnology , scaffold protein , phosphorylation , protein kinase a , biology , chemistry , signal transduction , biochemistry , in vitro
Akaps are A‐Kinase Anchoring Proteins that tether Protein Kinase A (PKA) and other enzymes to regulate a wide variety of cellular events by means of phosphorylation. Recent studies have suggested that members of the IQ motif GTPase Activating Proteins (IQGAP) gene family are important modulators of the actin cytoskeleton that ultimately regulate processes such as polarity, cell migration and neurite outgrowth. Here we hypothesized that AKAP220 acts as a scaffolding protein that tethers PKA and IQGAP2 to form a complex that promotes neurite outgrowth in a phosphorylation dependent manner. To test this hypothesis, we transfected primary hippocampal neurons and PC12 cells with cDNAs encoding different IQGAP2 phosphorylation mutants and measured neurite outgrowth upon neuronal differentiation. We found that PKA phosphorylates IQGAP2 in Thr716, and this is dependent on AKAP220 since its knockdown abolishes not only the phosphorylation of IQGAP2 but also the complex formed between these three proteins. Furthermore, the depletion of AKAP220 reduced neurite outgrowth in a similar manner than the IQGAP2 T716A mutant in PC12 cells, and reduced the length of the primary longest axon in primary hippocampal neurons. Taken together, these results indicate that AKAP220 modulates neurite outgrowth by acting as a scaffolding protein that regulates PKA‐mediated phosphorylation of IQGAP2 during neuronal differentiation.