3-Methyladenine specifically inhibits retrograde transport of cation-independent mannose 6-phosphate/insulin-like growth factor II receptor from the early endosome to the TGN.
3-Methyladenine (3-MA), a well-known inhibitor of autophagic sequestration, can also prevent class III phosphatidylinositide (PI) 3-kinase activity, which is required for many processes in endosomal membrane trafficking. Although much is known about the effects of other PI 3-kinase inhibitors, such as wortmannin and LY294002, on endosomal membrane trafficking, little is known about those of 3-MA. Here we show that the treatment of cells with 3-MA results in a specific redistribution of the cation-independent mannose 6-phosphate/insulin-like growth factor II receptor (MPR300) from the trans-Golgi network (TGN) to early/recycling endosomal compartments containing internalized transferrin. Importantly, in contrast to wortmannin and LY294002, 3-MA did not cause the enlargement of late endosomal/lysosomal compartments. The results suggest that the effect of 3-MA is restricted to the retrieval of MPR300 from early/recycling endosomes.
Hirosako
Kaori
K
Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan.
Imasato
Hiroshi
H
Hirota
Yuko
Y
Kuronita
Toshio
T
Masuyama
Naoko
N
Nishioka
Misa
M
Umeda
Atsushi
A
Fujita
Hideaki
H
Himeno
Masaru
M
Tanaka
Yoshitaka
Y
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002412:Cations / Q000378:metabolism; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D011992:Endosomes / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008360:Mannosephosphates / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D017527:Receptor, IGF Type 2 / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism; D000077191:Wortmannin; D021601:trans-Golgi Network / Q000378:metabolism*
D000730:Androstadienes; D002412:Cations; D002867:Chromones; D004791:Enzyme Inhibitors; C484953:MPR300 protein, rat; D008360:Mannosephosphates; D009025:Morpholines; D017527:Receptor, IGF Type 2; D014168:Transferrin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C025946:3-methyladenine; D019869:Phosphatidylinositol 3-Kinases; D000225:Adenine; D000077191:Wortmannin