RRC ID 55985
Author Moriwaki Y, Ohno Y, Ishii T, Takamura Y, Kita Y, Watabe K, Sango K, Tsuji S, Misawa H.
Title SIMPLE binds specifically to PI4P through SIMPLE-like domain and participates in protein trafficking in the trans-Golgi network and/or recycling endosomes.
Journal PLoS One
Abstract Small integral membrane protein of the lysosome/late endosome (SIMPLE) is a 161-amino acid cellular protein that contains a characteristic C-terminal domain known as the SIMPLE-like domain (SLD), which is well conserved among species. Several studies have demonstrated that SIMPLE localizes to the trans-Golgi network (TGN), early endosomes, lysosomes, multivesicular bodies, aggresomes and the plasma membrane. However, the amino acid regions responsible for its subcellular localization have not yet been identified. The SLD resembles the FYVE domain, which binds phosphatidylinositol (3)-phosphate (PI3P) and determines the subcellular localization of FYVE domain-containing proteins. In the present study, we have found that SIMPLE binds specifically to PI4P through its SLD. SIMPLE co-localized with PI4P and Rab11, a marker for recycling endosomes (REs, organelles enriched in PI4P) in both the IMS32 mouse Schwann cell line and Hela cells. Sucrose density-gradient centrifugation revealed that SIMPLE co-fractionated with syntaxin-6 (a TGN marker) and Rab11. We have also found that SIMPLE knockdown impeded recycling of transferrin and of transferrin receptor. Our overall results indicate that SIMPLE may regulate protein trafficking physiologically by localizing to the TGN and/or REs by binding PI4P.
Volume 13(6)
Pages e0199829
Published 2018-6-28
DOI 10.1371/journal.pone.0199829
PII PONE-D-17-26129
PMID 29953492
PMC PMC6023223
MeSH Animals Cell Line, Transformed DNA-Binding Proteins Endosomes / genetics Endosomes / metabolism* HeLa Cells Humans Mice Nuclear Proteins / genetics Nuclear Proteins / metabolism* Phosphatidylinositol Phosphates / genetics Phosphatidylinositol Phosphates / metabolism* Protein Domains Schwann Cells / metabolism* Transcription Factors / genetics Transcription Factors / metabolism* rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism trans-Golgi Network / genetics trans-Golgi Network / metabolism*
IF 2.776
Times Cited 1
Human and Animal Cells HeLa