title: Interaction between fidgetin and protein kinase A-anchoring protein AKAP95 is critical for palatogenesis in the mouse.
abstract: The gene defective in fidget mice encodes fidgetin, a member of the AAA (ATPases associated with diverse cellular activities) family of ATPases. Using a yeast two-hybrid screen, we identified cAMP-dependent protein kinase A anchoring protein 95 kDa (AKAP95) as a potential fidgetin-binding protein. Epitope-tagged fidgetin co-localized with endogenous AKAP95 in the nuclear matrix, and the physical interaction between fidgetin and AKAP95 was further confirmed by reciprocal immunoprecipitation. To evaluate the biological significance of the fidgetin-AKAP95 binding, we created AKAP95 mutant mice through a gene trap strategy. Akap95 mutant mice are surprisingly viable with no overt phenotype. However, a significant number of mice carrying both Akap95 and fidget mutations die soon after birth due to cleft palate, consistent with the overlapping expression of AKAP95 and fidgetin in the branchial arches during mouse embryogenesis. These results expand the spectrum of the pleiotropic phenotypes of fidget mice and provide new leads on the in vivo function of AKAP95.
authors.affiliation: Jackson Laboratory, Bar Harbor, Maine 04609.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Jackson Laboratory, Bar Harbor, Maine 04609.
authors.forename: Connie L
authors.initials: CL
authors.lastname: Mahaffey
authors.affiliation: Jackson Laboratory, Bar Harbor, Maine 04609.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bérubé
authors.affiliation: Jackson Laboratory, Bar Harbor, Maine 04609. Electronic address: wayne.frankel@jax.org.
authors.forename: Wayne N
authors.initials: WN
authors.lastname: Frankel
mesh_terms: D054758:A Kinase Anchor Proteins; D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002972:Cleft Palate / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins; D009024:Morphogenesis; D015530:Nuclear Matrix / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010159:Palate / Q000254:growth & development*; D010641:Phenotype; D011485:Protein Binding; D020798:Two-Hybrid System Techniques
chemical_list: D054758:A Kinase Anchor Proteins; C513988:Akap8 protein, mouse; D004268:DNA-Binding Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C498542:Fign protein, mouse