Apoptotic cleavage of rabaptin-5-like proteins and a model for rabaptin-5 inactivation in apoptosis.
Intracellular membrane transport from the plasma membrane is one of the processes affected in apoptotic cells. Apoptotic inhibition of endosomal transport occurs due to cleavage of Rabaptin-5, an effector of small GTPase Rab5, which results in inhibition of early endosome fusion. Recently several novel Rabaptin-5-like proteins were identified. We investigated whether Rabaptin-5-like proteins, Rabaptin-5gamma and Rabaptin-5delta, are also cleaved in apoptosis and found that both proteins are cleaved in apoptotic cell extracts by caspase-3-related proteases. This suggests that functional inactivation of these proteins is necessary for apoptotic cell death. We also mapped a novel, N-terminal, putative Rab5 binding site in Rabaptin-5-like proteins, which becomes physically separated from the previously known C-terminal Rab5 binding site after apoptotic cleavage of these proteins. Presence of the second Rab5 binding site provides a new insight into Rabaptin-5 function in early endosome fusion and a mechanistic model for functional inactivation of Rabaptin-5 in apoptosis.
Korobko
Elena V
EV
Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
Palgova
Irina V
IV
Kiselev
Sergey L
SL
Korobko
Igor V
IV
D000818:Animals; D017209:Apoptosis; D019556:COS Cells; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000502:physiology; D005047:Etoposide / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D008561:Membrane Fusion; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins / Q000235:genetics*; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D005047:Etoposide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020696:rab5 GTP-Binding Proteins