From Sorting Endosomes to Exocytosis: Association of Rab4 and Rab11 GTPases with the Fc Receptor, FcRn, during Recycling

E. Sally Ward,* Cruz Martinez,* Carlos Vaccaro,* Jinchun Zhou,* Qing Tang,* and Raimund J. Ober ${dagger}$

^*Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8576; Department of Electrical Engineering, University of Texas at Dallas, Richardson, TX 75080

Monitoring Editor: Suzanne Pfeffer

A longstanding question incell biology is how is the routing of intracellular organelleswithin cells regulated? Although data support the involvementof Rab4 and Rab11 GTPases in the recycling pathway, the functionof Rab11 in particular is uncertain. Here we have analyzed theassociation of these two Rab GTPases with the Fc receptor, FcRn,during intracellular trafficking. This Fc receptor is both functionallyand structurally distinct from the classical Fc ${gamma}$ receptors andtransports immunoglobulin (Ig) G (IgG) within cells. FcRn istherefore a recycling receptor that sorts bound IgG from unboundIgG in sorting endosomes. In the current study we have useddual color total internal reflection fluorescence microscopy(TIRFM) and wide field imaging of live cells to analyze theevents in human endothelial cells that are involved in the traffickingof FcRn positive (FcRn⁺) recycling compartments from sortingendosomes to exocytic sites at the plasma membrane. Our dataare consistent with the following model for this pathway: FcRnleaves sorting endosomes in Rab4⁺Rab11⁺ or Rab11⁺ compartments.For Rab4⁺Rab11⁺ compartments, Rab4 depletion occurs by segregationof the two Rab proteins into discrete domains that can separate.The Rab11⁺FcRn⁺ vesicle or tubule subsequently fuses with theplasma membrane in an exocytic event. In contrast to Rab11,Rab4 is not involved in exocytosis.

Address correspondence to: E. Sally Ward (sally.ward{at}utsouthwestern.edu)