Coupling of ER exit to microtubules through direct interaction of COPII with dynactin.
Transport of proteins from the endoplasmic reticulum (ER) to the Golgi is mediated by the sequential action of two coat complexes: COPII concentrates cargo for secretion at ER export sites, then COPI is subsequently recruited to nascent carriers and retrieves recycling proteins back to the ER. These carriers then move towards the Golgi along microtubules, driven by the dynein/dynactin complexes. Here we show that the Sec23p component of the COPII complex directly interacts with the dynactin complex through the carboxy-terminal cargo-binding domain of p150(Glued). Functional assays, including measurements of the rate of recycling of COPII on the ER membrane and quantitative analyses of secretion, indicate that this interaction underlies functional coupling of ER export to microtubules. Together, our data suggest a mechanism by which membranes of the early secretory pathway can be linked to motors and microtubules for subsequent organization and movement to the Golgi apparatus.
Watson
Peter
P
Department of Biochemistry, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.
Forster
Rebecca
R
Palmer
Krysten J
KJ
Pepperkok
Rainer
R
Stephens
David J
DJ
D000818:Animals; D001426:Bacterial Proteins; D022181:COP-Coated Vesicles / Q000378:metabolism*; D002522:Chlorocebus aethiops; D000072159:Dynactin Complex; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism / Q000648:ultrastructure; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D020409:Molecular Motor Proteins / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D012235:Rhodamines; D014404:Tubulin / Q000378:metabolism; D014709:Vero Cells; D033921:Vesicular Transport Proteins
D001426:Bacterial Proteins; C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D011506:Proteins; D012235:Rhodamines; C512739:SEC23A protein, human; D014404:Tubulin; D033921:Vesicular Transport Proteins; C054562:yellow fluorescent protein, Bacteria; D049452:Green Fluorescent Proteins