Glycosyl-Phosphatidyl-Inositol (GPI)-Anchors and Metalloproteases: Their Roles in the Regulation of Exosome Composition and NKG2D-Mediated Immune Recognition

Communication within the immune system depends on the release of factors that can travel and transmit information at points distant from the cell that produced them. In general, immune cells use two key strategies that can occur either at the plasma membrane or in intracellular compartments to produ...

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Detalles Bibliográficos
Autores: López-Cobo, Sheila, Campos-Silva, Carmen, Valés-Gómez, Mar
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universidad Loyola Andalucía
Repositorio:Brújula
OAI Identifier:oai:repositorio.uloyola.es:20.500.12412/5645
Acceso en línea:https://hdl.handle.net/20.500.12412/5645
Access Level:acceso abierto
Palabra clave:GPI-anchored proteins
Metalloproteases
DRMs
MICA/B
ULBP
Shedding
Exosomes
Immune evasion
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spelling Glycosyl-Phosphatidyl-Inositol (GPI)-Anchors and Metalloproteases: Their Roles in the Regulation of Exosome Composition and NKG2D-Mediated Immune RecognitionLópez-Cobo, SheilaCampos-Silva, CarmenValés-Gómez, MarGPI-anchored proteinsMetalloproteasesDRMsMICA/BULBPSheddingExosomesImmune evasionCommunication within the immune system depends on the release of factors that can travel and transmit information at points distant from the cell that produced them. In general, immune cells use two key strategies that can occur either at the plasma membrane or in intracellular compartments to produce such factors, vesicle release and proteolytic cleavage. Release of soluble factors in exosomes, a subset of vesicles that originate from intracellular compartments, depends generally on biochemical and lipid environment features. This physical environment allows proteins to be recruited to membrane microdomains that will be later endocytosed and further released to the extracellular milieu. Cholesterol and sphingolipid rich domains (also known as lipid rafts or detergent-resistant membranes, DRMs) often contribute to exosomes and these membrane regions are rich in proteins modified with Glycosyl-Phosphatidyl-Inositol (GPI) and lipids. For this reason, many palmitoylated and GPI-anchored proteins are preferentially recruited to exosomes. In this review, we analyse the biochemical features involved in the release of NKG2D-ligands as an example of functionally related gene families encoding both transmembrane and GPI-anchored proteins that can be released either by proteolysis or in exosomes, and modulate the intensity of the immune response. The immune receptor NKG2D is present in all human Natural Killer and T cells and plays an important role in the first barrier of defense against tumor and infection. However, tumor cells can evade the immune system by releasing NKG2D-ligands to induce down-regulation of the receptor. Some NKG2D-ligands can be recruited to exosomes and potently modulate receptor expression and immune function, while others are more susceptible to metalloprotease cleavage and are shed as soluble molecules. Strikingly, metalloprotease inhibition is sufficient to drive the accumulation in exosomes of ligands otherwise released by metalloprotease cleavage. In consequence, NKG2D-ligands appear as different entities in different cells, depending on cellular metabolism and biochemical structure, which mediate different intensities of immune modulation. We discuss whether similar mechanisms, depending on an interplay between metalloprotease cleavage and exosome release, could be a more general feature regulating the composition of exosomes released from human cells.2016info:eu-repo/semantics/articlehttps://hdl.handle.net/20.500.12412/5645reponame:Brújulainstname:Universidad Loyola AndalucíaInglésWork in the authors’ laboratory is supported by a grant from the Spanish Ministry of Economy and Competitivity (MINECO) [SAF2015-69169-R]. We would like to thank Dr. Hugh Reyburn for critically reading the manuscript. SL is a recipient of a FPU fellowship (MECD); CC is a recipient of a master’s fellowship from “Postgrado de la Fundación Ramón Areces-UAM.”http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uloyola.es:20.500.12412/56452026-06-24T12:48:37Z
dc.title.none.fl_str_mv Glycosyl-Phosphatidyl-Inositol (GPI)-Anchors and Metalloproteases: Their Roles in the Regulation of Exosome Composition and NKG2D-Mediated Immune Recognition
title Glycosyl-Phosphatidyl-Inositol (GPI)-Anchors and Metalloproteases: Their Roles in the Regulation of Exosome Composition and NKG2D-Mediated Immune Recognition
spellingShingle Glycosyl-Phosphatidyl-Inositol (GPI)-Anchors and Metalloproteases: Their Roles in the Regulation of Exosome Composition and NKG2D-Mediated Immune Recognition
López-Cobo, Sheila
GPI-anchored proteins
Metalloproteases
DRMs
MICA/B
ULBP
Shedding
Exosomes
Immune evasion
title_short Glycosyl-Phosphatidyl-Inositol (GPI)-Anchors and Metalloproteases: Their Roles in the Regulation of Exosome Composition and NKG2D-Mediated Immune Recognition
title_full Glycosyl-Phosphatidyl-Inositol (GPI)-Anchors and Metalloproteases: Their Roles in the Regulation of Exosome Composition and NKG2D-Mediated Immune Recognition
title_fullStr Glycosyl-Phosphatidyl-Inositol (GPI)-Anchors and Metalloproteases: Their Roles in the Regulation of Exosome Composition and NKG2D-Mediated Immune Recognition
title_full_unstemmed Glycosyl-Phosphatidyl-Inositol (GPI)-Anchors and Metalloproteases: Their Roles in the Regulation of Exosome Composition and NKG2D-Mediated Immune Recognition
title_sort Glycosyl-Phosphatidyl-Inositol (GPI)-Anchors and Metalloproteases: Their Roles in the Regulation of Exosome Composition and NKG2D-Mediated Immune Recognition
dc.creator.none.fl_str_mv López-Cobo, Sheila
Campos-Silva, Carmen
Valés-Gómez, Mar
author López-Cobo, Sheila
author_facet López-Cobo, Sheila
Campos-Silva, Carmen
Valés-Gómez, Mar
author_role author
author2 Campos-Silva, Carmen
Valés-Gómez, Mar
author2_role author
author
dc.subject.none.fl_str_mv GPI-anchored proteins
Metalloproteases
DRMs
MICA/B
ULBP
Shedding
Exosomes
Immune evasion
topic GPI-anchored proteins
Metalloproteases
DRMs
MICA/B
ULBP
Shedding
Exosomes
Immune evasion
description Communication within the immune system depends on the release of factors that can travel and transmit information at points distant from the cell that produced them. In general, immune cells use two key strategies that can occur either at the plasma membrane or in intracellular compartments to produce such factors, vesicle release and proteolytic cleavage. Release of soluble factors in exosomes, a subset of vesicles that originate from intracellular compartments, depends generally on biochemical and lipid environment features. This physical environment allows proteins to be recruited to membrane microdomains that will be later endocytosed and further released to the extracellular milieu. Cholesterol and sphingolipid rich domains (also known as lipid rafts or detergent-resistant membranes, DRMs) often contribute to exosomes and these membrane regions are rich in proteins modified with Glycosyl-Phosphatidyl-Inositol (GPI) and lipids. For this reason, many palmitoylated and GPI-anchored proteins are preferentially recruited to exosomes. In this review, we analyse the biochemical features involved in the release of NKG2D-ligands as an example of functionally related gene families encoding both transmembrane and GPI-anchored proteins that can be released either by proteolysis or in exosomes, and modulate the intensity of the immune response. The immune receptor NKG2D is present in all human Natural Killer and T cells and plays an important role in the first barrier of defense against tumor and infection. However, tumor cells can evade the immune system by releasing NKG2D-ligands to induce down-regulation of the receptor. Some NKG2D-ligands can be recruited to exosomes and potently modulate receptor expression and immune function, while others are more susceptible to metalloprotease cleavage and are shed as soluble molecules. Strikingly, metalloprotease inhibition is sufficient to drive the accumulation in exosomes of ligands otherwise released by metalloprotease cleavage. In consequence, NKG2D-ligands appear as different entities in different cells, depending on cellular metabolism and biochemical structure, which mediate different intensities of immune modulation. We discuss whether similar mechanisms, depending on an interplay between metalloprotease cleavage and exosome release, could be a more general feature regulating the composition of exosomes released from human cells.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12412/5645
url https://hdl.handle.net/20.500.12412/5645
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Work in the authors’ laboratory is supported by a grant from the Spanish Ministry of Economy and Competitivity (MINECO) [SAF2015-69169-R]. We would like to thank Dr. Hugh Reyburn for critically reading the manuscript. SL is a recipient of a FPU fellowship (MECD); CC is a recipient of a master’s fellowship from “Postgrado de la Fundación Ramón Areces-UAM.”
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:Brújula
instname:Universidad Loyola Andalucía
instname_str Universidad Loyola Andalucía
reponame_str Brújula
collection Brújula
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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