To move cargo between specific membrane-bound intracellular compartments, eukaryotic cells have evolved numerous mechanisms of membrane trafficking regulation. We found that CD1a, an MHC Class I-like lipid antigen presenting molecule follows an endocytic recycling pathway similar to that used by MHC Class I and other cargo internalized independently of clathrin. In an attempt to discover new regulators of this pathway, we screened a shRNA library for changes in CD1a surface expression and we found that the small GTPase Arl13b could be involved in the regulation of endocytic trafficking. The knock-down of Arl13b caused the clustering of early endosomes and the accumulation in this organelle of recycling cargo, such as transferrin, and also cargo destined for late endosomes and lysosomes, such as dextran. Moreover, the recycling rate of CD1a was decreased when Arl13b was knocked-down. Together, these results indicate that Arl13b regulates a sorting step from the early/sorting endosome. Arl13b belongs to the Arf-like (Arl) family of small GTPases, which remains poorly characterized. By uncovering its function we will shed light on the regulatory functions of this family of proteins. Future studies will focus on finding Arl13b effectors, determining if Arl13b binds to the cytoskeleton like other Arls, and also establishing the role of this protein in the primary cilium, a structure where Arl13b localizes prominently.
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