The retromer component SNX6 interacts with dynactin p150(Glued) and mediates endosome-to-TGN transport.
The retromer is a protein complex that mediates retrograde transport of transmembrane cargoes from endosomes to the trans-Golgi network (TGN). It is comprised of a cargo-selection subcomplex of Vps26, Vps29 and Vps35 and a membrane-binding coat subcomplex of sorting nexins (SNXs). Previous studies identified SNX1/2 as one of the components of the SNX subcomplex, and SNX5/6 as candidates for the second SNX. How the retromer-associated cargoes are recognized and transported by molecular motors are largely unknown. In this study, we found that one of SNX1/2's dimerization partners, SNX6, interacts with the p150(Glued) subunit of the dynein/dynactin motor complex. We present evidence that SNX6 is a component of the retromer, and that recruitment of the motor complex to the membrane-associated retromer requires the SNX6-p150(Glued) interaction. Disruption of the SNX6-p150(Glued) interaction causes failure in formation and detachment of the tubulovesicular sorting structures from endosomes and results in block of CI-MPR retrieval from endosomes to the TGN. These observations indicate that in addition to SNX1/2, SNX6 in association with the dynein/dynactin complex drives the formation and movement of tubular retrograde intermediates.
Hong
Zhi
Z
Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Yang
Yanrui
Y
Zhang
Cheng
C
Niu
Yang
Y
Li
Ke
K
Zhao
Xi
X
Liu
Jia-Jia
JJ
D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism; D011992:Endosomes / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008870:Microtubules / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D021381:Protein Transport / Q000502:physiology; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D021601:trans-Golgi Network / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; C513978:SNX1 protein, human; C431150:SNX6 protein, human; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; D004398:Dyneins