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Investigating the role of neuronal AKAP220 signaling complexes in cytoskeletal regulation during neurite outgrowth
Author(s) -
Lee Whiting Jennifer,
Tunquist Brian,
Scott John D.
Publication year - 2013
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.27.1_supplement.1036.3
Subject(s) - neurite , microbiology and biotechnology , cytoskeleton , biology , gene knockdown , signal transduction , kinase , phosphatase , cell , phosphorylation , cell culture , in vitro , biochemistry , genetics
Proper development and connectivity in the mammalian neocortex requires strict regulation of signaling, especially signals that impact cytoskeletal remodeling. A‐kinase anchoring proteins (AKAPs) are a diverse family of multivalent scaffolds that organize the signal cascades required for such precise cellular events. AKAP220 is widely expressed and anchors protein kinase A (PKA), glycogen synthase kinase 3 beta (GSK3β), and protein phosphatase 1 (PP1). This complex is also linked to the actin and microtubule networks through interactions with the IQGAP family of proteins. Knockdown of AKAP220 results in deficient cell migration and membrane outgrowth due to altered cytoskeletal dynamics. Although AKAP220 is expressed in brain, little is currently known about its neuronal function. We observe that knockdown of AKAP220 in Neuro‐2A cells increases average primary neurite length. Additionally, staining of mouse neurons in vitro reveals enrichment of AKAP220 in growth cones. Together, these results suggest this complex may regulate cytoskeletal events during neurite formation. To probe how each enzyme in the AKAP220 complex may regulate this process, specific enzyme binding regions have been mapped and deleted for use in future experiments. Additionally, we have developed AKAP220 conditional knockout mice to elucidate the biological significance of this complex during in vivo neocortical formation. Funding: NIH Pharmacological Sciences Training Grant: GM07750