Cytosolic phospholipase A2ε drives recycling through the clathrin-independent endocytic route

Mariagrazia Capestrano, Stefania Mariggio, Giuseppe Perinetti, Anastasia V. Egorova, Simona Iacobacci, Michele Santoro, Alessio Di Pentima, Cristiano Iurisci, Mikhail V. Egorov, Giuseppe Di Tullio, Roberto Buccione, Alberto Luini, Roman S. Polishchuk

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 languageEnglish
Pages (from-to)977-993
Number of pages17
JournalJournal of Cell Science
Volume127
Issue number5
DOIs
Publication statusPublished - Mar 2014

Fingerprint

Cytosolic Phospholipases A2
Clathrin
Recycling
Endosomes
Phospholipases A2
Enzymes
Membranes
Phosphatidylinositols
Lipids
Amino Acids
Growth

Keywords

  • Clathrin-independent endocytosis
  • Membrane curvature
  • MHC-I trafficking
  • Phospholipas A2
  • Recycling tubules

ASJC Scopus subject areas

  • Cell Biology

Cite this

Capestrano, M., Mariggio, S., Perinetti, G., Egorova, A. V., Iacobacci, S., Santoro, M., ... Polishchuk, R. S. (2014). Cytosolic phospholipase A2ε drives recycling through the clathrin-independent endocytic route. Journal of Cell Science, 127(5), 977-993. https://doi.org/10.1242/jcs.136598

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 journalArticle

Capestrano, M, Mariggio, S, Perinetti, G, Egorova, AV, Iacobacci, S, Santoro, M, Pentima, AD, Iurisci, C, Egorov, MV, Tullio, GD, Buccione, R, Luini, A & Polishchuk, RS 2014, 'Cytosolic phospholipase A2ε drives recycling through the clathrin-independent endocytic route', Journal of Cell Science, vol. 127, no. 5, pp. 977-993. https://doi.org/10.1242/jcs.136598
Capestrano M, Mariggio S, Perinetti G, Egorova AV, Iacobacci S, Santoro M et al. Cytosolic phospholipase A2ε drives recycling through the clathrin-independent endocytic route. Journal of Cell Science. 2014 Mar;127(5):977-993. https://doi.org/10.1242/jcs.136598
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. / Cytosolic phospholipase A2ε drives recycling through the clathrin-independent endocytic route. In: Journal of Cell Science. 2014 ; Vol. 127, No. 5. pp. 977-993.
@article{c080a480a0b7421f8274a3c087469e55,
title = "Cytosolic phospholipase A2ε drives recycling through the clathrin-independent endocytic route",
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.",
keywords = "Clathrin-independent endocytosis, Membrane curvature, MHC-I trafficking, Phospholipas A2, Recycling tubules",
author = "Mariagrazia Capestrano and Stefania Mariggio and Giuseppe Perinetti and Egorova, {Anastasia V.} and Simona Iacobacci and Michele Santoro and Pentima, {Alessio Di} and Cristiano Iurisci and Egorov, {Mikhail V.} and Tullio, {Giuseppe Di} and Roberto Buccione and Alberto Luini and Polishchuk, {Roman S.}",
year = "2014",
month = "3",
doi = "10.1242/jcs.136598",
language = "English",
volume = "127",
pages = "977--993",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "5",

}

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 -