Phosphatidylinositol 4,5-bisphosphate and Arf6-regulated membrane traffic
| Autor: | Fraser D. Brown, Tamas Balla, Andrew L. Rozelle, Julie G. Donaldson, Helen L. Yin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate ADP ribosylation factor Endosome Recombinant Fusion Proteins Nerve Tissue Proteins Endosomes Biology Transfection Models Biological Article Cell Line Cell membrane 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Genes Reporter medicine Animals Guanine Nucleotide Exchange Factors Humans Phosphatidylinositol 030304 developmental biology Arf6 membrane traffic phosphatidylinositol 4 5-bisphosphate PIP2 PIP 5-kinase 0303 health sciences ADP-Ribosylation Factors Cell Membrane Receptors Interleukin-2 Cell Biology Peptide Elongation Factors Transport protein Cell biology Protein Structure Tertiary Pleckstrin homology domain Isoenzymes Protein Transport medicine.anatomical_structure Phosphatidylinositol 4 5-bisphosphate chemistry Microscopy Fluorescence ADP-Ribosylation Factor 6 Type C Phospholipases lipids (amino acids peptides and proteins) Guanine nucleotide exchange factor Phospholipase C delta 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | ADP-ribosylation factor (Arf) 6 regulates the movement of membrane between the plasma membrane (PM) and a nonclathrin-derived endosomal compartment and activates phosphatidylinositol 4-phosphate 5-kinase (PIP 5-kinase), an enzyme that generates phosphatidylinositol 4,5-bisphosphate (PIP2). Here, we show that PIP2 visualized by expressing a fusion protein of the pleckstrin homology domain from PLCδ and green fluorescent protein (PH-GFP), colocalized with Arf6 at the PM and on tubular endosomal structures. Activation of Arf6 by expression of its exchange factor EFA6 stimulated protrusion formation, the uptake of PM into macropinosomes enriched in PIP2, and recycling of this membrane back to the PM. By contrast, expression of Arf6 Q67L, a GTP hydrolysis-resistant mutant, induced the formation of PIP2-positive actin-coated vacuoles that were unable to recycle membrane back to the PM. PM proteins, such as β1-integrin, plakoglobin, and major histocompatibility complex class I, that normally traffic through the Arf6 endosomal compartment became trapped in this vacuolar compartment. Overexpression of human PIP 5-kinase α mimicked the effects seen with Arf6 Q67L. These results demonstrate that PIP 5-kinase activity and PIP2 turnover controlled by activation and inactivation of Arf6 is critical for trafficking through the Arf6 PM-endosomal recycling pathway. |
| Databáze: | OpenAIRE |
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