D-AKAP2 interacts with Rab4 and Rab11 through its RGS domains and regulates transferrin receptor recycling.
Dual-specific A-kinase-anchoring protein 2 (D-AKAP2/AKAP10), which interacts at its carboxyl terminus with protein kinase A and PDZ domain proteins, contains two tandem regulator of G-protein signaling (RGS) domains for which the binding partners have remained unknown. We show here that these RGS domains interact with Rab11 and GTP-bound Rab4, the first demonstration of RGS domains binding small GTPases. Rab4 and Rab11 help regulate membrane trafficking through the endocytic recycling pathways by recruiting effector proteins to specific membrane domains. Although D-AKAP2 is primarily cytosolic in HeLa cells, a fraction of the protein localizes to endosomes and can be recruited there to a greater extent by overexpression of Rab4 or Rab11. D-AKAP2 also regulates the morphology of the Rab11-containing compartment, with co-expression causing accumulation of both proteins on enlarged endosomes. Knockdown of D-AKAP2 by RNA interference caused a redistribution of both Rab11 and the constitutively recycling transferrin receptor to the periphery of cells. Knockdown also caused an increase in the rate of transferrin recycling, suggesting that D-AKAP2 promotes accumulation of recycling proteins in the Rab4/Rab11-positive endocytic recycling compartment.
Department of Pharmacology, University of California at San Diego, La Jolla, California 92093, USA.
Christopher T
CT
Eggers
Jenny C
JC
Schafer
James R
JR
Goldenring
Susan S
SS
Taylor
D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011990:Receptors, Transferrin / Q000737:chemistry*; D014168:Transferrin / Q000737:chemistry; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D020695:rab4 GTP-Binding Proteins / Q000737:chemistry*; D000099193:rab11 GTP-Binding Proteins
D054758:A Kinase Anchor Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; D020691:rab GTP-Binding Proteins; D020695:rab4 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C484639:AKAP10 protein, human