Abstract
Previous studies have demonstrated that membrane tubulemediated transport events in biosynthetic and endocytic routes require phospholipase A2 (PLA2) activity. Here, we show that cytosolic phospholipase A2ε (cPLA2ε, also known as PLA2G4E) is targeted to the membrane compartments of the clathrinindependent endocytic route through a C-terminal stretch of positively charged amino acids, which allows the enzyme to interact with phosphoinositide lipids [especially PI(4,5)P2] that are enriched in clathrin-independent endosomes. Ablation of cPLA2ε suppressed the formation of tubular elements that carry internalized clathrin-independent cargoes, such as MHC-I, CD147 and CD55, back to the cell surface and, therefore, caused their intracellular retention. The ability of cPLA2ε to support recycling through tubule formation relies on the catalytic activity of the enzyme, because the inactive cPLA2εS420A mutant was not able to recover either tubule growth or transport from clathrin-independent endosomes. Taken together, our findings indicate that cPLA2ε is a new important regulator of trafficking processes within the clathrin-independent endocytic and recycling route. The affinity of cPLA2ε for this pathway supports a new hypothesis that different PLA2 enzymes use selective targeting mechanisms to regulate tubule formation locally during specific trafficking steps in the secretory and/or endocytic systems.
| Original language | English |
|---|---|
| Pages (from-to) | 977-993 |
| Number of pages | 17 |
| Journal | Journal of Cell Science |
| Volume | 127 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Mar 2014 |
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Keywords
- Clathrin-independent endocytosis
- Membrane curvature
- MHC-I trafficking
- Phospholipas A2
- Recycling tubules
ASJC Scopus subject areas
- Cell Biology
Cite this
Cytosolic phospholipase A2ε drives recycling through the clathrin-independent endocytic route. / Capestrano, Mariagrazia; Mariggio, Stefania; Perinetti, Giuseppe; Egorova, Anastasia V.; Iacobacci, Simona; Santoro, Michele; Pentima, Alessio Di; Iurisci, Cristiano; Egorov, Mikhail V.; Tullio, Giuseppe Di; Buccione, Roberto; Luini, Alberto; Polishchuk, Roman S.
In: Journal of Cell Science, Vol. 127, No. 5, 03.2014, p. 977-993.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cytosolic phospholipase A2ε drives recycling through the clathrin-independent endocytic route
AU - Capestrano, Mariagrazia
AU - Mariggio, Stefania
AU - Perinetti, Giuseppe
AU - Egorova, Anastasia V.
AU - Iacobacci, Simona
AU - Santoro, Michele
AU - Pentima, Alessio Di
AU - Iurisci, Cristiano
AU - Egorov, Mikhail V.
AU - Tullio, Giuseppe Di
AU - Buccione, Roberto
AU - Luini, Alberto
AU - Polishchuk, Roman S.
PY - 2014/3
Y1 - 2014/3
N2 - Previous studies have demonstrated that membrane tubulemediated transport events in biosynthetic and endocytic routes require phospholipase A2 (PLA2) activity. Here, we show that cytosolic phospholipase A2ε (cPLA2ε, also known as PLA2G4E) is targeted to the membrane compartments of the clathrinindependent endocytic route through a C-terminal stretch of positively charged amino acids, which allows the enzyme to interact with phosphoinositide lipids [especially PI(4,5)P2] that are enriched in clathrin-independent endosomes. Ablation of cPLA2ε suppressed the formation of tubular elements that carry internalized clathrin-independent cargoes, such as MHC-I, CD147 and CD55, back to the cell surface and, therefore, caused their intracellular retention. The ability of cPLA2ε to support recycling through tubule formation relies on the catalytic activity of the enzyme, because the inactive cPLA2εS420A mutant was not able to recover either tubule growth or transport from clathrin-independent endosomes. Taken together, our findings indicate that cPLA2ε is a new important regulator of trafficking processes within the clathrin-independent endocytic and recycling route. The affinity of cPLA2ε for this pathway supports a new hypothesis that different PLA2 enzymes use selective targeting mechanisms to regulate tubule formation locally during specific trafficking steps in the secretory and/or endocytic systems.
AB - Previous studies have demonstrated that membrane tubulemediated transport events in biosynthetic and endocytic routes require phospholipase A2 (PLA2) activity. Here, we show that cytosolic phospholipase A2ε (cPLA2ε, also known as PLA2G4E) is targeted to the membrane compartments of the clathrinindependent endocytic route through a C-terminal stretch of positively charged amino acids, which allows the enzyme to interact with phosphoinositide lipids [especially PI(4,5)P2] that are enriched in clathrin-independent endosomes. Ablation of cPLA2ε suppressed the formation of tubular elements that carry internalized clathrin-independent cargoes, such as MHC-I, CD147 and CD55, back to the cell surface and, therefore, caused their intracellular retention. The ability of cPLA2ε to support recycling through tubule formation relies on the catalytic activity of the enzyme, because the inactive cPLA2εS420A mutant was not able to recover either tubule growth or transport from clathrin-independent endosomes. Taken together, our findings indicate that cPLA2ε is a new important regulator of trafficking processes within the clathrin-independent endocytic and recycling route. The affinity of cPLA2ε for this pathway supports a new hypothesis that different PLA2 enzymes use selective targeting mechanisms to regulate tubule formation locally during specific trafficking steps in the secretory and/or endocytic systems.
KW - Clathrin-independent endocytosis
KW - Membrane curvature
KW - MHC-I trafficking
KW - Phospholipas A2
KW - Recycling tubules
UR - http://www.scopus.com/inward/record.url?scp=84896824639&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84896824639&partnerID=8YFLogxK
U2 - 10.1242/jcs.136598
DO - 10.1242/jcs.136598
M3 - Article
C2 - 24413173
AN - SCOPUS:84896824639
VL - 127
SP - 977
EP - 993
JO - Journal of Cell Science
JF - Journal of Cell Science
SN - 0021-9533
IS - 5
ER -