PDZ domains of Par-3 as potential phosphoinositide signaling integrators.
Multiple PDZ domain scaffold protein Par-3 and phosphoinositides (PIPs) are required for polarity in diverse cell types. We show that the second PDZ domain of Par-3 binds to phosphatidylinositol (PI) lipid membranes with high affinity. We further demonstrate that a large subset of PDZ domains in mammalian genomes are capable of binding to PI lipid membranes, indicating that lipid binding is the second most prevalent interaction mode of PDZ domains known to date. The biochemical and structural basis of Par-3 PDZ2-mediated membrane interaction is characterized in detail. The membrane binding capacity of Par-3 PDZ2 is critical for epithelial cell polarization. Interestingly, the lipid phosphatase PTEN directly binds to the third PDZ domain of Par-3. The concatenation of the PIP-binding PDZ2 and the lipid phosphatase PTEN-binding PDZ3 endows Par-3 as an ideal scaffold protein for integrating PIP signaling events during cellular polarization.
Wu
Hao
H
Department of Biochemistry, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, P.R. China.
Feng
Wei
W
Chen
Jia
J
Chan
Ling-Nga
LN
Huang
Siyi
S
Zhang
Mingjie
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D047468:Immunoprecipitation; D007668:Kidney / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009419:Nerve Tissue Proteins; D054731:PDZ Domains / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction
D002352:Carrier Proteins; D008051:Lipid Bilayers; D009419:Nerve Tissue Proteins; C472451:Pard3 protein, rat; D010716:Phosphatidylinositols; D034741:RNA, Small Interfering; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D002118:Calcium