Actin microfilaments facilitate the retrograde transport from the Golgi complex to the endoplasmic reticulum in mammalian cells.
The morphology and subcellular positioning of the Golgi complex depend on both microtubule and actin cytoskeletons. In contrast to microtubules, the role of actin cytoskeleton in the secretory pathway in mammalian cells has not been clearly established. Using cytochalasin D, we have previously shown that microfilaments are not involved in the endoplasmic reticulum-Golgi membrane dynamics. However, it has been reported that, unlike botulinum C2 toxin and latrunculins, cytochalasin D does not produce net depolymerization of actin filaments. Therefore, we have reassessed the functional role of actin microfilaments in the early steps of the biosynthetic pathway using C2 toxin and latrunculin B. The anterograde endoplasmic reticulum-to-Golgi transport monitored with the vesicular stomatitis virus-G protein remained unaltered in cells treated with cytochalasin D, latrunculin B or C2 toxin. Conversely, the brefeldin A-induced Golgi membrane fusion into the endoplasmic reticulum, the Golgi-to-endoplasmic reticulum transport of a Shiga toxin mutant form, and the subcellular distribution of the KDEL receptor were all impaired when actin microfilaments were depolymerized by latrunculin B or C2 toxin. These findings, together with the fact that COPI-coated and uncoated vesicles contain beta/gamma-actin isoforms, indicate that actin microfilaments are involved in the endoplasmic reticulum/Golgi interface, facilitating the retrograde Golgi-to-endoplasmic reticulum membrane transport, which could be mediated by the orchestrated movement of transport intermediates along microtubule and microfilament tracks.
Valderrama
F
F
Departament de Biologia Cel.lular i Anatomia Patològica, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, E-08036 Barcelona, Spain.
Durán
J M
JM
Babià
T
T
Barth
H
H
Renau-Piqueras
J
J
Egea
G
G
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001905:Botulinum Toxins / Q000494:pharmacology; D020126:Brefeldin A / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism*; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008322:Mammals / Q000378:metabolism; D008562:Membrane Glycoproteins; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D022621:Shiga Toxin / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014759:Viral Envelope Proteins / Q000378:metabolism*
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; C028391:G protein, vesicular stomatitis virus; C064459:KDEL receptor; D008562:Membrane Glycoproteins; D018000:Receptors, Peptide; D013844:Thiazoles; D053778:Thiazolidines; D014759:Viral Envelope Proteins; D020126:Brefeldin A; D015638:Cytochalasin D; D022621:Shiga Toxin; D001905:Botulinum Toxins; C096324:botulinum toxin type C; C037068:latrunculin B