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Lrp1/LDL receptor play critical roles in mannose 6-phosphate-independent lysosomal enzyme targeting

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Lrp1/LDL receptor play critical roles in mannose 6-phosphate-independent lysosomal enzyme targeting. / Markmann, Sandra; Thelen, Melanie; Cornils, Kerstin; Schweizer, Michaela; Brocke-Ahmadinejad, Nahal; Willnow, Thomas; Heeren, Joerg; Gieselmann, Volkmar; Braulke, Thomas; Kollmann, Katrin.

In: TRAFFIC, 18.03.2015.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Markmann, S, Thelen, M, Cornils, K, Schweizer, M, Brocke-Ahmadinejad, N, Willnow, T, Heeren, J, Gieselmann, V, Braulke, T & Kollmann, K 2015, 'Lrp1/LDL receptor play critical roles in mannose 6-phosphate-independent lysosomal enzyme targeting', TRAFFIC. https://doi.org/10.1111/tra.12284

APA

Markmann, S., Thelen, M., Cornils, K., Schweizer, M., Brocke-Ahmadinejad, N., Willnow, T., Heeren, J., Gieselmann, V., Braulke, T., & Kollmann, K. (2015). Lrp1/LDL receptor play critical roles in mannose 6-phosphate-independent lysosomal enzyme targeting. TRAFFIC. https://doi.org/10.1111/tra.12284

Vancouver

Markmann S, Thelen M, Cornils K, Schweizer M, Brocke-Ahmadinejad N, Willnow T et al. Lrp1/LDL receptor play critical roles in mannose 6-phosphate-independent lysosomal enzyme targeting. TRAFFIC. 2015 Mar 18. https://doi.org/10.1111/tra.12284

Bibtex

@article{c73bf2c4b8cc44bba452b1005b45fc12,
title = "Lrp1/LDL receptor play critical roles in mannose 6-phosphate-independent lysosomal enzyme targeting",
abstract = "Most lysosomal enzymes require mannose 6-phosphate (M6P) residues for efficient receptor-mediated lysosomal targeting. Although the lack of M6P residues results in missorting and hypersecretion, selected lysosomal enzymes reach normal levels in lysosomes of various cell types suggesting the existence of M6P-independent transport routes. Here, we quantify the lysosomal proteome in M6P-deficient mouse fibroblasts (PT(ki) ) using Stable Isotope Labeling by Amino acids in Cell culture (SILAC)-based comparative mass spectrometry, and find unchanged amounts of 20 % of lysosomal enzymes, including cathepsin D and B (Ctsd, Ctsb). Examination of fibroblasts from a new mouse line lacking both M6P and sortilin, a candidate for M6P-independent transport of lysosomal enzymes, revealed that sortilin does not act as cargo receptor for Ctsb and Ctsd. Using fibroblast lines deficient for endocytic lipoprotein receptors we could demonstrate that both LDL receptor and Lrp1 mediate the internalization of non-phosphorylated Ctsb and Ctsd. Furthermore, the presence of Lrp1 inhibitor increased the secretion of Ctsd from PT(ki) cells. These findings establish Lrp1 and LDL receptors in M6P-independent secretion-recapture targeting mechanism for lysosomal enzymes.",
author = "Sandra Markmann and Melanie Thelen and Kerstin Cornils and Michaela Schweizer and Nahal Brocke-Ahmadinejad and Thomas Willnow and Joerg Heeren and Volkmar Gieselmann and Thomas Braulke and Katrin Kollmann",
note = "This article is protected by copyright. All rights reserved.",
year = "2015",
month = mar,
day = "18",
doi = "10.1111/tra.12284",
language = "English",
journal = "TRAFFIC",
issn = "1398-9219",
publisher = "Blackwell Munksgaard",

}

RIS

TY - JOUR

T1 - Lrp1/LDL receptor play critical roles in mannose 6-phosphate-independent lysosomal enzyme targeting

AU - Markmann, Sandra

AU - Thelen, Melanie

AU - Cornils, Kerstin

AU - Schweizer, Michaela

AU - Brocke-Ahmadinejad, Nahal

AU - Willnow, Thomas

AU - Heeren, Joerg

AU - Gieselmann, Volkmar

AU - Braulke, Thomas

AU - Kollmann, Katrin

N1 - This article is protected by copyright. All rights reserved.

PY - 2015/3/18

Y1 - 2015/3/18

N2 - Most lysosomal enzymes require mannose 6-phosphate (M6P) residues for efficient receptor-mediated lysosomal targeting. Although the lack of M6P residues results in missorting and hypersecretion, selected lysosomal enzymes reach normal levels in lysosomes of various cell types suggesting the existence of M6P-independent transport routes. Here, we quantify the lysosomal proteome in M6P-deficient mouse fibroblasts (PT(ki) ) using Stable Isotope Labeling by Amino acids in Cell culture (SILAC)-based comparative mass spectrometry, and find unchanged amounts of 20 % of lysosomal enzymes, including cathepsin D and B (Ctsd, Ctsb). Examination of fibroblasts from a new mouse line lacking both M6P and sortilin, a candidate for M6P-independent transport of lysosomal enzymes, revealed that sortilin does not act as cargo receptor for Ctsb and Ctsd. Using fibroblast lines deficient for endocytic lipoprotein receptors we could demonstrate that both LDL receptor and Lrp1 mediate the internalization of non-phosphorylated Ctsb and Ctsd. Furthermore, the presence of Lrp1 inhibitor increased the secretion of Ctsd from PT(ki) cells. These findings establish Lrp1 and LDL receptors in M6P-independent secretion-recapture targeting mechanism for lysosomal enzymes.

AB - Most lysosomal enzymes require mannose 6-phosphate (M6P) residues for efficient receptor-mediated lysosomal targeting. Although the lack of M6P residues results in missorting and hypersecretion, selected lysosomal enzymes reach normal levels in lysosomes of various cell types suggesting the existence of M6P-independent transport routes. Here, we quantify the lysosomal proteome in M6P-deficient mouse fibroblasts (PT(ki) ) using Stable Isotope Labeling by Amino acids in Cell culture (SILAC)-based comparative mass spectrometry, and find unchanged amounts of 20 % of lysosomal enzymes, including cathepsin D and B (Ctsd, Ctsb). Examination of fibroblasts from a new mouse line lacking both M6P and sortilin, a candidate for M6P-independent transport of lysosomal enzymes, revealed that sortilin does not act as cargo receptor for Ctsb and Ctsd. Using fibroblast lines deficient for endocytic lipoprotein receptors we could demonstrate that both LDL receptor and Lrp1 mediate the internalization of non-phosphorylated Ctsb and Ctsd. Furthermore, the presence of Lrp1 inhibitor increased the secretion of Ctsd from PT(ki) cells. These findings establish Lrp1 and LDL receptors in M6P-independent secretion-recapture targeting mechanism for lysosomal enzymes.

U2 - 10.1111/tra.12284

DO - 10.1111/tra.12284

M3 - SCORING: Journal article

C2 - 25786328

JO - TRAFFIC

JF - TRAFFIC

SN - 1398-9219

ER -