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A dileucine motif and a cluster of acidic amino acids in the second cytoplasmic domain of the batten disease-related CLN3 protein are required for efficient lysosomal targeting

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A dileucine motif and a cluster of acidic amino acids in the second cytoplasmic domain of the batten disease-related CLN3 protein are required for efficient lysosomal targeting. / Storch, Stephan; Pohl, Sandra; Braulke, Thomas.

in: J BIOL CHEM, Jahrgang 279, Nr. 51, 17.12.2004, S. 53625-34.

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

Harvard

Storch, S, Pohl, S & Braulke, T 2004, 'A dileucine motif and a cluster of acidic amino acids in the second cytoplasmic domain of the batten disease-related CLN3 protein are required for efficient lysosomal targeting', J BIOL CHEM, Jg. 279, Nr. 51, S. 53625-34. https://doi.org/10.1074/jbc.M410930200

APA

Storch, S., Pohl, S., & Braulke, T. (2004). A dileucine motif and a cluster of acidic amino acids in the second cytoplasmic domain of the batten disease-related CLN3 protein are required for efficient lysosomal targeting. J BIOL CHEM, 279(51), 53625-34. https://doi.org/10.1074/jbc.M410930200

Vancouver

Storch S, Pohl S, Braulke T. A dileucine motif and a cluster of acidic amino acids in the second cytoplasmic domain of the batten disease-related CLN3 protein are required for efficient lysosomal targeting. J BIOL CHEM. 2004 Dez 17;279(51):53625-34. https://doi.org/10.1074/jbc.M410930200

Bibtex

@article{28fa3f1971ac4cde8d48d6a2229145e4,
title = "A dileucine motif and a cluster of acidic amino acids in the second cytoplasmic domain of the batten disease-related CLN3 protein are required for efficient lysosomal targeting",
abstract = "The juvenile form of ceroid lipofuscinosis (Batten disease) is a neurodegenerative lysosomal storage disorder caused by mutations in the CLN3 gene. CLN3 encodes a multimembrane-spanning protein of unknown function, which is mainly localized in lysosomes in non-neuronal cells and in endosomes in neuronal cells. For this study we constructed chimeric proteins of three CLN3 cytoplasmic domains fused to the lumenal and transmembrane domains of the reporter proteins LAMP-1 and lysosomal acid phosphatase to identify lysosomal targeting motifs and to determine the intracellular transport and subcellular localization of the chimera in transfected cell lines. We report that a novel type of dileucine-based sorting motif, EEEX(8)LI, present in the second cytoplasmic domain of CLN3, is sufficient for proper targeting to lysosomes. The first cytoplasmic domain of CLN3 and the mutation of the dileucine motif resulted in a partial missorting of chimeric proteins to the plasma membrane. At equilibrium, 4-13% of the different chimera are present at the cell surface. Analysis of lysosome-specific proteolytic processing revealed that lysosomal acid phosphatase chimera containing the second cytoplasmic domain of CLN3 showed the highest rate of lysosomal delivery, whereas the C terminus of CLN3 was found to be less efficient in lysosomal targeting. However, none of these cytosolic CLN3 domains was able to interact with AP-1, AP-3, or GGA3 adaptor complexes. These data revealed that lysosomal sorting motifs located in an intramolecular cytoplasmic domain of a multimembrane-spanning protein have different structural requirements for adaptor binding than sorting signals found in the C-terminal cytoplasmic domains of single- or dual-spanning lysosomal membrane proteins.",
keywords = "Acid Phosphatase, Amino Acid Motifs, Amino Acid Sequence, Amino Acids, Animals, Antigens, CD, Biotinylation, Blotting, Western, Brain, CHO Cells, Cell Membrane, Cricetinae, Cytoplasm, Cytosol, DNA, Complementary, Genetic Vectors, Glutathione Transferase, HeLa Cells, Humans, Immunoprecipitation, Leucine, Lysosome-Associated Membrane Glycoproteins, Lysosomes, Membrane Glycoproteins, Microscopy, Fluorescence, Molecular Chaperones, Molecular Sequence Data, Protein Structure, Tertiary, Protein Transport, Recombinant Fusion Proteins, Transfection",
author = "Stephan Storch and Sandra Pohl and Thomas Braulke",
year = "2004",
month = dec,
day = "17",
doi = "10.1074/jbc.M410930200",
language = "English",
volume = "279",
pages = "53625--34",
journal = "J BIOL CHEM",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "51",

}

RIS

TY - JOUR

T1 - A dileucine motif and a cluster of acidic amino acids in the second cytoplasmic domain of the batten disease-related CLN3 protein are required for efficient lysosomal targeting

AU - Storch, Stephan

AU - Pohl, Sandra

AU - Braulke, Thomas

PY - 2004/12/17

Y1 - 2004/12/17

N2 - The juvenile form of ceroid lipofuscinosis (Batten disease) is a neurodegenerative lysosomal storage disorder caused by mutations in the CLN3 gene. CLN3 encodes a multimembrane-spanning protein of unknown function, which is mainly localized in lysosomes in non-neuronal cells and in endosomes in neuronal cells. For this study we constructed chimeric proteins of three CLN3 cytoplasmic domains fused to the lumenal and transmembrane domains of the reporter proteins LAMP-1 and lysosomal acid phosphatase to identify lysosomal targeting motifs and to determine the intracellular transport and subcellular localization of the chimera in transfected cell lines. We report that a novel type of dileucine-based sorting motif, EEEX(8)LI, present in the second cytoplasmic domain of CLN3, is sufficient for proper targeting to lysosomes. The first cytoplasmic domain of CLN3 and the mutation of the dileucine motif resulted in a partial missorting of chimeric proteins to the plasma membrane. At equilibrium, 4-13% of the different chimera are present at the cell surface. Analysis of lysosome-specific proteolytic processing revealed that lysosomal acid phosphatase chimera containing the second cytoplasmic domain of CLN3 showed the highest rate of lysosomal delivery, whereas the C terminus of CLN3 was found to be less efficient in lysosomal targeting. However, none of these cytosolic CLN3 domains was able to interact with AP-1, AP-3, or GGA3 adaptor complexes. These data revealed that lysosomal sorting motifs located in an intramolecular cytoplasmic domain of a multimembrane-spanning protein have different structural requirements for adaptor binding than sorting signals found in the C-terminal cytoplasmic domains of single- or dual-spanning lysosomal membrane proteins.

AB - The juvenile form of ceroid lipofuscinosis (Batten disease) is a neurodegenerative lysosomal storage disorder caused by mutations in the CLN3 gene. CLN3 encodes a multimembrane-spanning protein of unknown function, which is mainly localized in lysosomes in non-neuronal cells and in endosomes in neuronal cells. For this study we constructed chimeric proteins of three CLN3 cytoplasmic domains fused to the lumenal and transmembrane domains of the reporter proteins LAMP-1 and lysosomal acid phosphatase to identify lysosomal targeting motifs and to determine the intracellular transport and subcellular localization of the chimera in transfected cell lines. We report that a novel type of dileucine-based sorting motif, EEEX(8)LI, present in the second cytoplasmic domain of CLN3, is sufficient for proper targeting to lysosomes. The first cytoplasmic domain of CLN3 and the mutation of the dileucine motif resulted in a partial missorting of chimeric proteins to the plasma membrane. At equilibrium, 4-13% of the different chimera are present at the cell surface. Analysis of lysosome-specific proteolytic processing revealed that lysosomal acid phosphatase chimera containing the second cytoplasmic domain of CLN3 showed the highest rate of lysosomal delivery, whereas the C terminus of CLN3 was found to be less efficient in lysosomal targeting. However, none of these cytosolic CLN3 domains was able to interact with AP-1, AP-3, or GGA3 adaptor complexes. These data revealed that lysosomal sorting motifs located in an intramolecular cytoplasmic domain of a multimembrane-spanning protein have different structural requirements for adaptor binding than sorting signals found in the C-terminal cytoplasmic domains of single- or dual-spanning lysosomal membrane proteins.

KW - Acid Phosphatase

KW - Amino Acid Motifs

KW - Amino Acid Sequence

KW - Amino Acids

KW - Animals

KW - Antigens, CD

KW - Biotinylation

KW - Blotting, Western

KW - Brain

KW - CHO Cells

KW - Cell Membrane

KW - Cricetinae

KW - Cytoplasm

KW - Cytosol

KW - DNA, Complementary

KW - Genetic Vectors

KW - Glutathione Transferase

KW - HeLa Cells

KW - Humans

KW - Immunoprecipitation

KW - Leucine

KW - Lysosome-Associated Membrane Glycoproteins

KW - Lysosomes

KW - Membrane Glycoproteins

KW - Microscopy, Fluorescence

KW - Molecular Chaperones

KW - Molecular Sequence Data

KW - Protein Structure, Tertiary

KW - Protein Transport

KW - Recombinant Fusion Proteins

KW - Transfection

U2 - 10.1074/jbc.M410930200

DO - 10.1074/jbc.M410930200

M3 - SCORING: Journal article

C2 - 15469932

VL - 279

SP - 53625

EP - 53634

JO - J BIOL CHEM

JF - J BIOL CHEM

SN - 0021-9258

IS - 51

ER -