title: Arl13b regulates endocytic recycling traffic.
abstract: Intracellular recycling pathways play critical roles in internalizing membrane and fluid phase cargo and in balancing the inflow and outflow of membrane and cell surface molecules. To identify proteins involved in the regulation of endocytic recycling, we used an shRNA trafficking library and screened for changes in the surface expression of CD1a antigen-presenting molecules that follow an endocytic recycling route. We found that silencing of the ADP-ribosylation factor (Arf)-like small GTPase Arl13b led to a decrease in CD1a surface expression, diminished CD1a function, and delayed CD1a recycling, suggesting that Arl13b is involved in the regulation of endocytic recycling traffic. Arl13b appears to be required for the major route of endocytic trafficking, causing clustering of early endosomes and leading to the accumulation of endocytic cargo. Moreover, Arl13b colocalized with markers of the endocytic recycling pathway followed by CD1a, namely Arf6 and Rab22a. We also detected an interaction between Arl13b and the actin cytoskeleton. Arl13b was previously implicated in cilia formation and function. Our present results indicate a previously unidentified role for Arl13b in endocytic recycling traffic and suggest a link between Arl13b function and the actin cytoskeleton.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. duarte.barral@fcm.unl.pt
authors.forename: Duarte C
authors.initials: DC
authors.lastname: Barral
authors.forename: Salil
authors.initials: S
authors.lastname: Garg
authors.forename: Cristina
authors.initials: C
authors.lastname: Casalou
authors.forename: Gerald F M
authors.initials: GF
authors.lastname: Watts
authors.forename: José L
authors.initials: JL
authors.lastname: Sandoval
authors.forename: José S
authors.initials: JS
authors.lastname: Ramalho
authors.forename: Victor W
authors.initials: VW
authors.lastname: Hsu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brenner
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000737:chemistry / Q000378:metabolism*; D008841:Actin Cytoskeleton / Q000378:metabolism; D018949:Antigens, CD1 / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D016000:Cluster Analysis; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D020868:Gene Silencing; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D050505:Mutant Proteins / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D014168:Transferrin / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000089982:ADP-Ribosylation Factor 6; D018949:Antigens, CD1; C419393:CD1a antigen; D050505:Mutant Proteins; C484191:RAB22A protein, human; D014168:Transferrin; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; C530391:ARL13B protein, human; D020691:rab GTP-Binding Proteins