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The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain.

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The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain. / Schneppenheim, Janna; Dressel, Ralf; Hüttl, Susann; Lüllmann-Rauch, Renate; Engelke, Michael; Dittmann, Kai; Wienands, Jürgen; Eskelinen, Eeva-Liisa; Hermans-Borgmeyer, Irmgard; Fluhrer, Regina; Saftig, Paul; Schröder, Bernd.

in: J EXP MED, Jahrgang 210, Nr. 1, 1, 2013, S. 41-58.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Schneppenheim, J, Dressel, R, Hüttl, S, Lüllmann-Rauch, R, Engelke, M, Dittmann, K, Wienands, J, Eskelinen, E-L, Hermans-Borgmeyer, I, Fluhrer, R, Saftig, P & Schröder, B 2013, 'The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain.', J EXP MED, Jg. 210, Nr. 1, 1, S. 41-58. <http://www.ncbi.nlm.nih.gov/pubmed/23267015?dopt=Citation>

APA

Schneppenheim, J., Dressel, R., Hüttl, S., Lüllmann-Rauch, R., Engelke, M., Dittmann, K., Wienands, J., Eskelinen, E-L., Hermans-Borgmeyer, I., Fluhrer, R., Saftig, P., & Schröder, B. (2013). The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain. J EXP MED, 210(1), 41-58. [1]. http://www.ncbi.nlm.nih.gov/pubmed/23267015?dopt=Citation

Vancouver

Schneppenheim J, Dressel R, Hüttl S, Lüllmann-Rauch R, Engelke M, Dittmann K et al. The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain. J EXP MED. 2013;210(1):41-58. 1.

Bibtex

@article{932dd840a0d944e380320bbebd0c2f2e,
title = "The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain.",
abstract = "Regulated intramembrane proteolysis is a central cellular process involved in signal transduction and membrane protein turnover. The presenilin homologue signal-peptide-peptidase-like 2a (SPPL2a) has been implicated in the cleavage of type 2 transmembrane proteins. We show that the invariant chain (li, CD74) of the major histocompatability class II complex (MHCII) undergoes intramembrane proteolysis mediated by SPPL2a. B lymphocytes of SPPL2a(-/-) mice accumulate an N-terminal fragment (NTF) of CD74, which severely impairs membrane traffic within the endocytic system and leads to an altered response to B cell receptor stimulation, reduced BAFF-R surface expression, and accumulation of MHCII in transitional developmental stage T1 B cells. This results in significant loss of B cell subsets beyond the T1 stage and disrupted humoral immune responses, which can be recovered by additional ablation of CD74. Hence, we provide evidence that regulation of CD74-NTF levels by SPPL2a is indispensable for B cell development and function by maintaining trafficking and integrity of MHCII-containing endosomes, highlighting SPPL2a as a promising pharmacological target for depleting and/or modulating B cells.",
keywords = "Animals, Humans, Cells, Cultured, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Protein Transport, Molecular Sequence Data, Base Sequence, Cell Survival/genetics, Endosomes/*metabolism, Membrane Proteins/genetics/*metabolism, Peptide Fragments/metabolism, Antigens, Differentiation, B-Lymphocyte/genetics/*metabolism, Aspartic Acid Endopeptidases/genetics/*metabolism, B-Cell Activation Factor Receptor/genetics/metabolism, B-Lymphocyte Subsets/metabolism, B-Lymphocytes/immunology/pathology/*physiology/ultrastructure, Histocompatibility Antigens Class II/genetics/*metabolism, Immunity, Humoral/genetics, Vacuoles/metabolism, Animals, Humans, Cells, Cultured, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Protein Transport, Molecular Sequence Data, Base Sequence, Cell Survival/genetics, Endosomes/*metabolism, Membrane Proteins/genetics/*metabolism, Peptide Fragments/metabolism, Antigens, Differentiation, B-Lymphocyte/genetics/*metabolism, Aspartic Acid Endopeptidases/genetics/*metabolism, B-Cell Activation Factor Receptor/genetics/metabolism, B-Lymphocyte Subsets/metabolism, B-Lymphocytes/immunology/pathology/*physiology/ultrastructure, Histocompatibility Antigens Class II/genetics/*metabolism, Immunity, Humoral/genetics, Vacuoles/metabolism",
author = "Janna Schneppenheim and Ralf Dressel and Susann H{\"u}ttl and Renate L{\"u}llmann-Rauch and Michael Engelke and Kai Dittmann and J{\"u}rgen Wienands and Eeva-Liisa Eskelinen and Irmgard Hermans-Borgmeyer and Regina Fluhrer and Paul Saftig and Bernd Schr{\"o}der",
year = "2013",
language = "English",
volume = "210",
pages = "41--58",
journal = "J EXP MED",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "1",

}

RIS

TY - JOUR

T1 - The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain.

AU - Schneppenheim, Janna

AU - Dressel, Ralf

AU - Hüttl, Susann

AU - Lüllmann-Rauch, Renate

AU - Engelke, Michael

AU - Dittmann, Kai

AU - Wienands, Jürgen

AU - Eskelinen, Eeva-Liisa

AU - Hermans-Borgmeyer, Irmgard

AU - Fluhrer, Regina

AU - Saftig, Paul

AU - Schröder, Bernd

PY - 2013

Y1 - 2013

N2 - Regulated intramembrane proteolysis is a central cellular process involved in signal transduction and membrane protein turnover. The presenilin homologue signal-peptide-peptidase-like 2a (SPPL2a) has been implicated in the cleavage of type 2 transmembrane proteins. We show that the invariant chain (li, CD74) of the major histocompatability class II complex (MHCII) undergoes intramembrane proteolysis mediated by SPPL2a. B lymphocytes of SPPL2a(-/-) mice accumulate an N-terminal fragment (NTF) of CD74, which severely impairs membrane traffic within the endocytic system and leads to an altered response to B cell receptor stimulation, reduced BAFF-R surface expression, and accumulation of MHCII in transitional developmental stage T1 B cells. This results in significant loss of B cell subsets beyond the T1 stage and disrupted humoral immune responses, which can be recovered by additional ablation of CD74. Hence, we provide evidence that regulation of CD74-NTF levels by SPPL2a is indispensable for B cell development and function by maintaining trafficking and integrity of MHCII-containing endosomes, highlighting SPPL2a as a promising pharmacological target for depleting and/or modulating B cells.

AB - Regulated intramembrane proteolysis is a central cellular process involved in signal transduction and membrane protein turnover. The presenilin homologue signal-peptide-peptidase-like 2a (SPPL2a) has been implicated in the cleavage of type 2 transmembrane proteins. We show that the invariant chain (li, CD74) of the major histocompatability class II complex (MHCII) undergoes intramembrane proteolysis mediated by SPPL2a. B lymphocytes of SPPL2a(-/-) mice accumulate an N-terminal fragment (NTF) of CD74, which severely impairs membrane traffic within the endocytic system and leads to an altered response to B cell receptor stimulation, reduced BAFF-R surface expression, and accumulation of MHCII in transitional developmental stage T1 B cells. This results in significant loss of B cell subsets beyond the T1 stage and disrupted humoral immune responses, which can be recovered by additional ablation of CD74. Hence, we provide evidence that regulation of CD74-NTF levels by SPPL2a is indispensable for B cell development and function by maintaining trafficking and integrity of MHCII-containing endosomes, highlighting SPPL2a as a promising pharmacological target for depleting and/or modulating B cells.

KW - Animals

KW - Humans

KW - Cells, Cultured

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Mutant Strains

KW - Protein Transport

KW - Molecular Sequence Data

KW - Base Sequence

KW - Cell Survival/genetics

KW - Endosomes/metabolism

KW - Membrane Proteins/genetics/metabolism

KW - Peptide Fragments/metabolism

KW - Antigens, Differentiation, B-Lymphocyte/genetics/metabolism

KW - Aspartic Acid Endopeptidases/genetics/metabolism

KW - B-Cell Activation Factor Receptor/genetics/metabolism

KW - B-Lymphocyte Subsets/metabolism

KW - B-Lymphocytes/immunology/pathology/physiology/ultrastructure

KW - Histocompatibility Antigens Class II/genetics/metabolism

KW - Immunity, Humoral/genetics

KW - Vacuoles/metabolism

KW - Animals

KW - Humans

KW - Cells, Cultured

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Mutant Strains

KW - Protein Transport

KW - Molecular Sequence Data

KW - Base Sequence

KW - Cell Survival/genetics

KW - Endosomes/metabolism

KW - Membrane Proteins/genetics/metabolism

KW - Peptide Fragments/metabolism

KW - Antigens, Differentiation, B-Lymphocyte/genetics/metabolism

KW - Aspartic Acid Endopeptidases/genetics/metabolism

KW - B-Cell Activation Factor Receptor/genetics/metabolism

KW - B-Lymphocyte Subsets/metabolism

KW - B-Lymphocytes/immunology/pathology/physiology/ultrastructure

KW - Histocompatibility Antigens Class II/genetics/metabolism

KW - Immunity, Humoral/genetics

KW - Vacuoles/metabolism

M3 - SCORING: Journal article

VL - 210

SP - 41

EP - 58

JO - J EXP MED

JF - J EXP MED

SN - 0022-1007

IS - 1

M1 - 1

ER -