Publication

Serine Phosphorylation of L-Selectin Regulates ERM Binding, Clustering, and Monocyte Protrusion in Transendothelial Migration

Newe, A., Rzeniewicz, K., Konig, M., Schroer, C. F. E., Joachim, J., Rey-Gallardo, A., Marrink, S. J., Deka, J., Parsons, M. & Ivetic, A., 25-Sep-2019, In : Frontiers in Immunology. 10, 18 p., 2227.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Newe, A., Rzeniewicz, K., Konig, M., Schroer, C. F. E., Joachim, J., Rey-Gallardo, A., Marrink, S. J., Deka, J., Parsons, M., & Ivetic, A. (2019). Serine Phosphorylation of L-Selectin Regulates ERM Binding, Clustering, and Monocyte Protrusion in Transendothelial Migration. Frontiers in Immunology, 10, [2227]. https://doi.org/10.3389/fimmu.2019.02227

Author

Newe, Abigail ; Rzeniewicz, Karolina ; Konig, Melanie ; Schroer, Carsten F. E. ; Joachim, Justin ; Rey-Gallardo, Angela ; Marrink, Siewert J. ; Deka, Jurgen ; Parsons, Maddy ; Ivetic, Aleksandar. / Serine Phosphorylation of L-Selectin Regulates ERM Binding, Clustering, and Monocyte Protrusion in Transendothelial Migration. In: Frontiers in Immunology. 2019 ; Vol. 10.

Harvard

Newe, A, Rzeniewicz, K, Konig, M, Schroer, CFE, Joachim, J, Rey-Gallardo, A, Marrink, SJ, Deka, J, Parsons, M & Ivetic, A 2019, 'Serine Phosphorylation of L-Selectin Regulates ERM Binding, Clustering, and Monocyte Protrusion in Transendothelial Migration', Frontiers in Immunology, vol. 10, 2227. https://doi.org/10.3389/fimmu.2019.02227

Standard

Serine Phosphorylation of L-Selectin Regulates ERM Binding, Clustering, and Monocyte Protrusion in Transendothelial Migration. / Newe, Abigail; Rzeniewicz, Karolina; Konig, Melanie; Schroer, Carsten F. E.; Joachim, Justin; Rey-Gallardo, Angela; Marrink, Siewert J.; Deka, Jurgen; Parsons, Maddy; Ivetic, Aleksandar.

In: Frontiers in Immunology, Vol. 10, 2227, 25.09.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Newe A, Rzeniewicz K, Konig M, Schroer CFE, Joachim J, Rey-Gallardo A et al. Serine Phosphorylation of L-Selectin Regulates ERM Binding, Clustering, and Monocyte Protrusion in Transendothelial Migration. Frontiers in Immunology. 2019 Sep 25;10. 2227. https://doi.org/10.3389/fimmu.2019.02227


BibTeX

@article{128d92e5674549a882cb71157dc6693d,
title = "Serine Phosphorylation of L-Selectin Regulates ERM Binding, Clustering, and Monocyte Protrusion in Transendothelial Migration",
abstract = "The migration of circulating leukocytes toward damaged tissue is absolutely fundamental to the inflammatory response, and transendothelial migration (TEM) describes the first cellular barrier that is breached in this process. Human CD14(+) inflammatory monocytes express L-selectin, bestowing a non-canonical role in invasion during TEM. In vivo evidence supports a role for L-selectin in regulating TEM and chemotaxis, but the intracellular mechanism is poorly understood. The ezrin-radixin-moesin (ERM) proteins anchor transmembrane proteins to the cortical actin-based cytoskeleton and additionally act as signaling adaptors. During TEM, the L-selectin tail within transmigrating pseudopods interacts first with ezrin to transduce signals for protrusion, followed by moesin to drive ectodomain shedding of L-selectin to limit protrusion. Collectively, interaction of L-selectin with ezrin and moesin fine-tunes monocyte protrusive behavior in TEM. Using FLIM/FRET approaches, we show that ERM binding is absolutely required for outside-in L-selectin clustering. The cytoplasmic tail of human L-selectin contains two serine (S) residues at positions 364 and 367, and here we show that they play divergent roles in regulating ERM binding. Phospho-S364 blocks direct interaction with ERM, whereas molecular modeling suggests phospho-S367 likely drives desorption of the L-selectin tail from the inner leaflet of the plasma membrane to potentiate ERM binding. Serine-to-alanine mutagenesis of S367, but not S364, significantly reduced monocyte protrusive behavior in TEM under flow conditions. Our data propose a model whereby L-selectin tail desorption from the inner leaflet of the plasma membrane and ERM binding are two separable steps that collectively regulate protrusive behavior in TEM.",
keywords = "forster resonance energy transfer (FRET), fluorescence lifetime imaging microscopy (FLIM), molecular dynamics, extravasation, diapedesis, MEMBRANE-PROXIMAL CLEAVAGE, MARTINI FORCE-FIELD, LEUKOCYTE MIGRATION, MOLECULAR-DYNAMICS, LIPID RAFTS, CYTOPLASMIC DOMAIN, CROSS-LINKING, FERM DOMAIN, IN-VIVO, ADHESION",
author = "Abigail Newe and Karolina Rzeniewicz and Melanie Konig and Schroer, {Carsten F. E.} and Justin Joachim and Angela Rey-Gallardo and Marrink, {Siewert J.} and Jurgen Deka and Maddy Parsons and Aleksandar Ivetic",
year = "2019",
month = sep,
day = "25",
doi = "10.3389/fimmu.2019.02227",
language = "English",
volume = "10",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media SA",

}

RIS

TY - JOUR

T1 - Serine Phosphorylation of L-Selectin Regulates ERM Binding, Clustering, and Monocyte Protrusion in Transendothelial Migration

AU - Newe, Abigail

AU - Rzeniewicz, Karolina

AU - Konig, Melanie

AU - Schroer, Carsten F. E.

AU - Joachim, Justin

AU - Rey-Gallardo, Angela

AU - Marrink, Siewert J.

AU - Deka, Jurgen

AU - Parsons, Maddy

AU - Ivetic, Aleksandar

PY - 2019/9/25

Y1 - 2019/9/25

N2 - The migration of circulating leukocytes toward damaged tissue is absolutely fundamental to the inflammatory response, and transendothelial migration (TEM) describes the first cellular barrier that is breached in this process. Human CD14(+) inflammatory monocytes express L-selectin, bestowing a non-canonical role in invasion during TEM. In vivo evidence supports a role for L-selectin in regulating TEM and chemotaxis, but the intracellular mechanism is poorly understood. The ezrin-radixin-moesin (ERM) proteins anchor transmembrane proteins to the cortical actin-based cytoskeleton and additionally act as signaling adaptors. During TEM, the L-selectin tail within transmigrating pseudopods interacts first with ezrin to transduce signals for protrusion, followed by moesin to drive ectodomain shedding of L-selectin to limit protrusion. Collectively, interaction of L-selectin with ezrin and moesin fine-tunes monocyte protrusive behavior in TEM. Using FLIM/FRET approaches, we show that ERM binding is absolutely required for outside-in L-selectin clustering. The cytoplasmic tail of human L-selectin contains two serine (S) residues at positions 364 and 367, and here we show that they play divergent roles in regulating ERM binding. Phospho-S364 blocks direct interaction with ERM, whereas molecular modeling suggests phospho-S367 likely drives desorption of the L-selectin tail from the inner leaflet of the plasma membrane to potentiate ERM binding. Serine-to-alanine mutagenesis of S367, but not S364, significantly reduced monocyte protrusive behavior in TEM under flow conditions. Our data propose a model whereby L-selectin tail desorption from the inner leaflet of the plasma membrane and ERM binding are two separable steps that collectively regulate protrusive behavior in TEM.

AB - The migration of circulating leukocytes toward damaged tissue is absolutely fundamental to the inflammatory response, and transendothelial migration (TEM) describes the first cellular barrier that is breached in this process. Human CD14(+) inflammatory monocytes express L-selectin, bestowing a non-canonical role in invasion during TEM. In vivo evidence supports a role for L-selectin in regulating TEM and chemotaxis, but the intracellular mechanism is poorly understood. The ezrin-radixin-moesin (ERM) proteins anchor transmembrane proteins to the cortical actin-based cytoskeleton and additionally act as signaling adaptors. During TEM, the L-selectin tail within transmigrating pseudopods interacts first with ezrin to transduce signals for protrusion, followed by moesin to drive ectodomain shedding of L-selectin to limit protrusion. Collectively, interaction of L-selectin with ezrin and moesin fine-tunes monocyte protrusive behavior in TEM. Using FLIM/FRET approaches, we show that ERM binding is absolutely required for outside-in L-selectin clustering. The cytoplasmic tail of human L-selectin contains two serine (S) residues at positions 364 and 367, and here we show that they play divergent roles in regulating ERM binding. Phospho-S364 blocks direct interaction with ERM, whereas molecular modeling suggests phospho-S367 likely drives desorption of the L-selectin tail from the inner leaflet of the plasma membrane to potentiate ERM binding. Serine-to-alanine mutagenesis of S367, but not S364, significantly reduced monocyte protrusive behavior in TEM under flow conditions. Our data propose a model whereby L-selectin tail desorption from the inner leaflet of the plasma membrane and ERM binding are two separable steps that collectively regulate protrusive behavior in TEM.

KW - forster resonance energy transfer (FRET)

KW - fluorescence lifetime imaging microscopy (FLIM)

KW - molecular dynamics

KW - extravasation

KW - diapedesis

KW - MEMBRANE-PROXIMAL CLEAVAGE

KW - MARTINI FORCE-FIELD

KW - LEUKOCYTE MIGRATION

KW - MOLECULAR-DYNAMICS

KW - LIPID RAFTS

KW - CYTOPLASMIC DOMAIN

KW - CROSS-LINKING

KW - FERM DOMAIN

KW - IN-VIVO

KW - ADHESION

U2 - 10.3389/fimmu.2019.02227

DO - 10.3389/fimmu.2019.02227

M3 - Article

VL - 10

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 2227

ER -

ID: 98534724