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PMID: 16291863 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Phospholipase D2 is required for efficient endocytic recycling of transferrin receptors.

Molecular biology of the cell ·Vol. 17 ·No. 2 ·2006-02-00 ·Pages 598-606

Padrón D, Tall RD, Roth MG

Abstract

RNA interference-mediated depletion of phospholipase D2 (PLD2), but not PLD1, inhibited recycling of transferrin receptors in HeLa cells, whereas the internalization rate was unaffected by depletion of either PLD. Although reduction of both PLD isoforms inhibits PLD activity stimulated by phorbol 12-myristic 13-acetate, only depletion of PLD2 decreased nonstimulated activity. Cells with reduced PLD2 accumulated a greater fraction of transferrin receptors in a perinuclear compartment that was positive for Rab11, a marker of recycling endosomes. EFA6, an exchange factor for Arf6, has been proposed to stimulate the recycling of transferrin receptors. Thus, one consequence of EFA6 overexpression would be a reduction of the internal pool of receptors. We confirmed this observation in control HeLa cells; however, overexpression of EFA6 failed to decrease the internal pool of transferrin receptors that accumulate in cells previously depleted of PLD2. These observations suggest that either PLD2 is required for a constitutive Arf6-mediated recycling pathway or in the absence of PLD2 transferrin receptors accumulate in recycling endosomes that are not responsive to overexpression of EFA6.

MeSH Terms
ADP-Ribosylation Factor 6 ADP-Ribosylation Factors/physiology Cell Membrane/metabolism Endocytosis/physiology Endosomes/metabolism Gene Expression Regulation/drug effects Guanine Nucleotide Exchange Factors HeLa Cells Humans Nerve Tissue Proteins/metabolism Phosphatidylinositol 4,5-Diphosphate/biosynthesis Phospholipase D/antagonists & inhibitors,genetics,physiology Phosphotransferases (Alcohol Group Acceptor)/metabolism RNA Interference Receptors, Transferrin/metabolism Tetradecanoylphorbol Acetate/pharmacology rab GTP-Binding Proteins/metabolism
Chemicals
ADP-Ribosylation Factor 6 Guanine Nucleotide Exchange Factors Nerve Tissue Proteins PSD protein, human Phosphatidylinositol 4,5-Diphosphate Receptors, Transferrin Phosphotransferases (Alcohol Group Acceptor) phospholipase D2 Phospholipase D phospholipase D1 rab11 protein ADP-Ribosylation Factors ARF6 protein, human rab GTP-Binding Proteins Tetradecanoylphorbol Acetate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Padrón David
Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9038.
Tall Renee D
Roth Michael G
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e05-05-0389
Published
2006-02-00
Epub
2005-00-16
Pages
598-606
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC1356572
Subset
IM
Grants
NCRR NIH HHS · C06 RR015437 · United States
NCRR NIH HHS · C06 RR-15437 · United States
External Links
PubMed source DOI: 10.1091/mbc.e05-05-0389 PMC Full Text View journal details
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