CART: an Hrs/actinin-4/BERP/myosin V protein complex required for efficient receptor recycling.
Altering the number of surface receptors can rapidly modulate cellular responses to extracellular signals. Some receptors, like the transferrin receptor (TfR), are constitutively internalized and recycled to the plasma membrane. Other receptors, like the epidermal growth factor receptor (EGFR), are internalized after ligand binding and then ultimately degraded in the lysosome. Routing internalized receptors to different destinations suggests that distinct molecular mechanisms may direct their movement. Here, we report that the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation. The hrs/actinin-4/BERP/myosin V (CART [cytoskeleton-associated recycling or transport]) complex assembles in a linear manner and interrupting binding of any member to its neighbor produces an inhibition of transferrin recycling rate. Disrupting the CART complex results in shunting receptors to a slower recycling pathway that involves the recycling endosome. The novel CART complex may provide a molecular mechanism for the actin-dependence of rapid recycling of constitutively recycled plasma membrane receptors.
Yan
Qing
Q
Department of Neurobiology and Anatomy, University of Texas Medical School, Houston, TX 77030, USA.
Sun
Wei
W
Kujala
Pekka
P
Lotfi
Yasmin
Y
Vida
Thomas A
TA
Bean
Andrew J
AJ
D000185:Actinin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004247:DNA / Q000235:genetics; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008840:Microfilament Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D008954:Models, Biological; D046912:Multiprotein Complexes; D024701:Myosin Type V / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
C111453:ACTN4 protein, human; D002352:Carrier Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D008840:Microfilament Proteins; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; C426543:TRIM3 protein, human; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate; D000185:Actinin; D004247:DNA; D066246:ErbB Receptors; D024701:Myosin Type V