title: SNX4 coordinates endosomal sorting of TfnR with dynein-mediated transport into the endocytic recycling compartment.
abstract: SNX-BAR proteins are a sub-family of sorting nexins implicated in endosomal sorting. Here, we establish that through its phox homology (PX) and Bin-Amphiphysin-Rvs (BAR) domains, sorting nexin-4 (SNX4) is associated with tubular and vesicular elements of a compartment that overlaps with peripheral early endosomes and the juxtanuclear endocytic recycling compartment (ERC). Suppression of SNX4 perturbs transport between these compartments and causes lysosomal degradation of the transferrin receptor (TfnR). Through an interaction with KIBRA, a protein previously shown to bind dynein light chain 1, we establish that SNX4 associates with the minus end-directed microtubule motor dynein. Although suppression of KIBRA and dynein perturbs early endosome-to-ERC transport, TfnR sorting is maintained. We propose that by driving membrane tubulation, SNX4 coordinates iterative, geometric-based sorting of the TfnR with the long-range transport of carriers from early endosomes to the ERC. Finally, these data suggest that by associating with molecular motors, SNX-BAR proteins may coordinate sorting with carrier transport between donor and recipient membranes.
authors.affiliation: The Henry Wellcome Integrated Signalling Laboratories, Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Traer
authors.forename: Anna C
authors.initials: AC
authors.lastname: Rutherford
authors.forename: Krysten J
authors.initials: KJ
authors.lastname: Palmer
authors.forename: Thomas
authors.initials: T
authors.lastname: Wassmer
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Oakley
authors.forename: Naomi
authors.initials: N
authors.lastname: Attar
authors.forename: Jez G
authors.initials: JG
authors.lastname: Carlton
authors.forename: Joachim
authors.initials: J
authors.lastname: Kremerskothen
authors.forename: David J
authors.initials: DJ
authors.lastname: Stephens
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cullen
mesh_terms: D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D004398:Dyneins / Q000502:physiology*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008870:Microtubules / Q000378:metabolism; D010750:Phosphoproteins; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism*; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011506:Proteins; D011990:Receptors, Transferrin; C513981:SNX4 protein, human; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; C513637:WWC1 protein, human; D004398:Dyneins