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A Ceramide-Regulated Element in the Late Endosomal Protein LAPTM4B Controls Amino Acid Transporter Interaction

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A Ceramide-Regulated Element in the Late Endosomal Protein LAPTM4B Controls Amino Acid Transporter Interaction. / Zhou, Kecheng; Dichlberger, Andrea; Martinez-Seara, Hector; Nyholm, Thomas K.M.; Li, Shiqian; Kim, Young Ah; Vattulainen, Ilpo; Ikonen, Elina; Blom, Tomas.

In: ACS Central Science, Vol. 4, No. 5, 23.05.2018, p. 548-558.

Research output: Contribution to journalArticleScientificpeer-review

Harvard

Zhou, K, Dichlberger, A, Martinez-Seara, H, Nyholm, TKM, Li, S, Kim, YA, Vattulainen, I, Ikonen, E & Blom, T 2018, 'A Ceramide-Regulated Element in the Late Endosomal Protein LAPTM4B Controls Amino Acid Transporter Interaction', ACS Central Science, vol. 4, no. 5, pp. 548-558. https://doi.org/10.1021/acscentsci.7b00582

APA

Zhou, K., Dichlberger, A., Martinez-Seara, H., Nyholm, T. K. M., Li, S., Kim, Y. A., ... Blom, T. (2018). A Ceramide-Regulated Element in the Late Endosomal Protein LAPTM4B Controls Amino Acid Transporter Interaction. ACS Central Science, 4(5), 548-558. https://doi.org/10.1021/acscentsci.7b00582

Vancouver

Zhou K, Dichlberger A, Martinez-Seara H, Nyholm TKM, Li S, Kim YA et al. A Ceramide-Regulated Element in the Late Endosomal Protein LAPTM4B Controls Amino Acid Transporter Interaction. ACS Central Science. 2018 May 23;4(5):548-558. https://doi.org/10.1021/acscentsci.7b00582

Author

Zhou, Kecheng ; Dichlberger, Andrea ; Martinez-Seara, Hector ; Nyholm, Thomas K.M. ; Li, Shiqian ; Kim, Young Ah ; Vattulainen, Ilpo ; Ikonen, Elina ; Blom, Tomas. / A Ceramide-Regulated Element in the Late Endosomal Protein LAPTM4B Controls Amino Acid Transporter Interaction. In: ACS Central Science. 2018 ; Vol. 4, No. 5. pp. 548-558.

Bibtex - Download

@article{ea52c151d7cd455082a3f50633b54de1,
title = "A Ceramide-Regulated Element in the Late Endosomal Protein LAPTM4B Controls Amino Acid Transporter Interaction",
abstract = "Membrane proteins are functionally regulated by the composition of the surrounding lipid bilayer. The late endosomal compartment is a central site for the generation of ceramide, a bioactive sphingolipid, which regulates responses to cell stress. The molecular interactions between ceramide and late endosomal transmembrane proteins are unknown. Here, we uncover in atomistic detail the ceramide interaction of Lysosome Associated Protein Transmembrane 4B (LAPTM4B), implicated in ceramide-dependent cell death and autophagy, and its functional relevance in lysosomal nutrient signaling. The ceramide-mediated regulation of LAPTM4B depends on a sphingolipid interaction motif and an adjacent aspartate residue in the protein's third transmembrane (TM3) helix. The interaction motif provides the preferred contact points for ceramide while the neighboring membrane-embedded acidic residue confers flexibility that is subject to ceramide-induced conformational changes, reducing TM3 bending. This facilitates the interaction between LAPTM4B and the amino acid transporter heavy chain 4F2hc, thereby controlling mTORC signaling. These findings provide mechanistic insights into how transmembrane proteins sense and respond to ceramide.",
author = "Kecheng Zhou and Andrea Dichlberger and Hector Martinez-Seara and Nyholm, {Thomas K.M.} and Shiqian Li and Kim, {Young Ah} and Ilpo Vattulainen and Elina Ikonen and Tomas Blom",
year = "2018",
month = "5",
day = "23",
doi = "10.1021/acscentsci.7b00582",
language = "English",
volume = "4",
pages = "548--558",
journal = "ACS Central Science",
issn = "2374-7943",
publisher = "American Chemical Society",
number = "5",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - A Ceramide-Regulated Element in the Late Endosomal Protein LAPTM4B Controls Amino Acid Transporter Interaction

AU - Zhou, Kecheng

AU - Dichlberger, Andrea

AU - Martinez-Seara, Hector

AU - Nyholm, Thomas K.M.

AU - Li, Shiqian

AU - Kim, Young Ah

AU - Vattulainen, Ilpo

AU - Ikonen, Elina

AU - Blom, Tomas

PY - 2018/5/23

Y1 - 2018/5/23

N2 - Membrane proteins are functionally regulated by the composition of the surrounding lipid bilayer. The late endosomal compartment is a central site for the generation of ceramide, a bioactive sphingolipid, which regulates responses to cell stress. The molecular interactions between ceramide and late endosomal transmembrane proteins are unknown. Here, we uncover in atomistic detail the ceramide interaction of Lysosome Associated Protein Transmembrane 4B (LAPTM4B), implicated in ceramide-dependent cell death and autophagy, and its functional relevance in lysosomal nutrient signaling. The ceramide-mediated regulation of LAPTM4B depends on a sphingolipid interaction motif and an adjacent aspartate residue in the protein's third transmembrane (TM3) helix. The interaction motif provides the preferred contact points for ceramide while the neighboring membrane-embedded acidic residue confers flexibility that is subject to ceramide-induced conformational changes, reducing TM3 bending. This facilitates the interaction between LAPTM4B and the amino acid transporter heavy chain 4F2hc, thereby controlling mTORC signaling. These findings provide mechanistic insights into how transmembrane proteins sense and respond to ceramide.

AB - Membrane proteins are functionally regulated by the composition of the surrounding lipid bilayer. The late endosomal compartment is a central site for the generation of ceramide, a bioactive sphingolipid, which regulates responses to cell stress. The molecular interactions between ceramide and late endosomal transmembrane proteins are unknown. Here, we uncover in atomistic detail the ceramide interaction of Lysosome Associated Protein Transmembrane 4B (LAPTM4B), implicated in ceramide-dependent cell death and autophagy, and its functional relevance in lysosomal nutrient signaling. The ceramide-mediated regulation of LAPTM4B depends on a sphingolipid interaction motif and an adjacent aspartate residue in the protein's third transmembrane (TM3) helix. The interaction motif provides the preferred contact points for ceramide while the neighboring membrane-embedded acidic residue confers flexibility that is subject to ceramide-induced conformational changes, reducing TM3 bending. This facilitates the interaction between LAPTM4B and the amino acid transporter heavy chain 4F2hc, thereby controlling mTORC signaling. These findings provide mechanistic insights into how transmembrane proteins sense and respond to ceramide.

U2 - 10.1021/acscentsci.7b00582

DO - 10.1021/acscentsci.7b00582

M3 - Article

VL - 4

SP - 548

EP - 558

JO - ACS Central Science

JF - ACS Central Science

SN - 2374-7943

IS - 5

ER -