Mannose 6 phosphorylation of lysosomal enzymes controls B cell functions
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Mannose 6 phosphorylation of lysosomal enzymes controls B cell functions. / Otomo, Takanobu; Schweizer, Michaela; Kollmann, Katrin; Schumacher, Valéa; Muschol, Nicole; Tolosa, Eva; Mittrücker, Hans-Willi; Braulke, Thomas.
In: J CELL BIOL, Vol. 208, No. 2, 19.01.2015, p. 171-80.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Mannose 6 phosphorylation of lysosomal enzymes controls B cell functions
AU - Otomo, Takanobu
AU - Schweizer, Michaela
AU - Kollmann, Katrin
AU - Schumacher, Valéa
AU - Muschol, Nicole
AU - Tolosa, Eva
AU - Mittrücker, Hans-Willi
AU - Braulke, Thomas
N1 - © 2015 Otomo et al.
PY - 2015/1/19
Y1 - 2015/1/19
N2 - Antigen processing and presentation and cytotoxic targeting depend on the activities of several lysosomal enzymes that require mannose 6-phosphate (M6P) sorting signals for efficient intracellular transport and localization. In this paper, we show that mice deficient in the formation of M6P residues exhibit significant loss of cathepsin proteases in B cells, leading to lysosomal dysfunction with accumulation of storage material, impaired antigen processing and presentation, and subsequent defects in B cell maturation and antibody production. The targeting of lysosomal and granular enzymes lacking M6P residues is less affected in dendritic cells and T cells and sufficient for maintenance of degradative and lytic functions. M6P deficiency also impairs serum immunoglobulin levels and antibody responses to vaccination in patients. Our data demonstrate the critical role of M6P-dependent transport routes for B cell functions in vivo and humoral immunity in mice and human.
AB - Antigen processing and presentation and cytotoxic targeting depend on the activities of several lysosomal enzymes that require mannose 6-phosphate (M6P) sorting signals for efficient intracellular transport and localization. In this paper, we show that mice deficient in the formation of M6P residues exhibit significant loss of cathepsin proteases in B cells, leading to lysosomal dysfunction with accumulation of storage material, impaired antigen processing and presentation, and subsequent defects in B cell maturation and antibody production. The targeting of lysosomal and granular enzymes lacking M6P residues is less affected in dendritic cells and T cells and sufficient for maintenance of degradative and lytic functions. M6P deficiency also impairs serum immunoglobulin levels and antibody responses to vaccination in patients. Our data demonstrate the critical role of M6P-dependent transport routes for B cell functions in vivo and humoral immunity in mice and human.
U2 - 10.1083/jcb.201407077
DO - 10.1083/jcb.201407077
M3 - SCORING: Journal article
C2 - 25601403
VL - 208
SP - 171
EP - 180
JO - J CELL BIOL
JF - J CELL BIOL
SN - 0021-9525
IS - 2
ER -