Alterations of tau and VASP during microcystin-LR-induced cytoskeletal reorganization in a human liver cell line.
Previously, we have reported alterations to HSP27 during Microcystin-LR (MC-LR)-induced cytoskeletal reorganization in the human liver cell line HL7702. To further elucidate the detailed mechanism of MC-LR-induced cytoskeletal assembly, we focused on two cytoskeletal-related proteins, Tau and VASP. These two proteins phosphorylated status influences their ability to bind and stabilize cytoskeleton. We found that MC-LR markedly increased the level of Tau phosphorylation with the dissociation of phosphorylated Tau from the cytoskeleton. Furthermore, the phosphorylation of Tau induced by MC-LR was suppressed by an activator of PP2A and by an inhibitor of p38 MAPK. VASP was also hyperphosphorylated upon MC-LR exposure; however, its phosphorylation appeared to regulate its cellular localization rather than cytoskeletal dynamics, and its phosphorylation was unaffected by the PP2A activator. These data suggest that phosphorylated Tau is regulated by p38 MAPK, possibly as a consequence of PP2A inhibition. Tau hyperphosphorylation is likely an important factor leading to the cytoskeletal destabilization triggered by MC-LR and the role of VASP alteration upon MC-LR exposure needs to be studied further. To our knowledge, the finding that Tau is implicated in cytoskeletal destabilization in MC-LR-treated hepatocytes and MC-LR-induced VASP's alteration has not been reported previously.
Department of Biochemistry, School of Medicine, Zhejiang University, Hangzhou, 310058, People's Republic of China.
Yu
Y
Sun
Jing-hui
JH
Liu
Pu
P
Huang
Zong-lou
ZL
Guo
Li-hong
LH
Xu
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008387:Marine Toxins; D052998:Microcystins / Q000633:toxicity*; D008840:Microfilament Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D055551:HSP27 Heat-Shock Proteins; C054369:MAPT protein, human; D008387:Marine Toxins; D052998:Microcystins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D016875:tau Proteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D048051:p38 Mitogen-Activated Protein Kinases; C057862:cyanoginosin LR
HL7702; Microcystin-LR; PP2A; Tau; VASP