Cytoplasmic microtubules are essential for the formation of membrane-bound polyribosomes.
Colchicine, at low intracellular concentrations, causes a rapid depolymerization of membrane-associated polyribosomes. Poly(A+) mRNA is rapidly lost from these polysomes, and 80 S monomers are left attached to the membranes of the endoplasmic reticulum. Binding studies and measurements of intracellular colchicine concentrations indicate that the drug is acting via depolymerization of cytoplasmic microtubules. The vinca alkaloids, vincristine and vinblastine, have the same effect on polyribosomes, whereas lumicolchicine is ineffective. Furthermore, cordycepin and actinomycin D are without effect on polyribosomes indicating that colchicine is not simply inhibiting the production or transport of new mRNA. It appears that disruption of the cytoplasmic microtubule network prevents membrane-associated ribosomes from reinitiating protein synthesis resulting in the rapid loss of mRNA.
Walker
P R
PR
Whitfield
J F
JF
D000818:Animals; D002850:Chromatography, Gel; D003078:Colchicine / Q000494:pharmacology; D003593:Cytoplasm / Q000648:ultrastructure*; D008162:Lumicolchicines / Q000494:pharmacology; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000502:physiology*; D011061:Poly A / Q000378:metabolism; D011132:Polyribosomes / Q000648:ultrastructure*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014404:Tubulin / Q000378:metabolism; D014747:Vinblastine / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D008162:Lumicolchicines; D012333:RNA, Messenger; D012335:RNA, Ribosomal; D014404:Tubulin; C044176:poly(A) ribosomal RNA; D011061:Poly A; D014750:Vincristine; D014747:Vinblastine; D003078:Colchicine