Distinct reading of different structural determinants modulates the dileucine-mediated transport steps of the lysosomal membrane protein LIMPII and the insulin-sensitive glucose transporter GLUT4

I V Sandoval, S Martinez-Arca, J Valdueza, S Palacios, G D Holman

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Abstract

Leucine-based motifs mediate the sorting of membrane proteins at such cellular sites as the trans-Golgi network, endosomes, and plasma membrane. A Leu paired with a second Leu, He, or Met, while itself lacking the ability to mediate transport, is the key structural feature in these motifs, Here we have studied the structural differences between the leucine-based motifs contained in the COOH tails of LIMPII and GLUT4, two membrane proteins that are transported through the secretory pathway and are targeted to lysosomes (1-3) and to a perinuclear compartment adjacent to the Golgi complex (4), respectively. LIMPII and GLUT4 display negatively (Asp(470)/Glu(471)) and positively (Arg(484)/Ar-485) charged residues, respectively, at positions -4 and -5 upstream from the critical Leu residue. The change in the charge sign of residues -4 and -5 results in missorting of LIMPII and GLUT4. We note that the acidic Glu residue at position -4 is critical for efficient intracellular sorting of LIMPII to lysosomes, but is dispensable for its surface internalization by endocytosis. Efficient intracellular sorting and endocytosis of GLUT4 require an Arg pair between positions -4 and -7. These results are consistent with the existence of distinct leucine-based motifs and provide evidence of their different readings at different cellular sites.
Original languageEnglish
Pages (from-to)39874-39885
Number of pages12
JournalJournal of Biological Chemistry
Volume275
Issue number51
Publication statusPublished - 2000

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Lysosome-Associated Membrane Glycoproteins
Facilitative Glucose Transport Proteins
Sorting
Leucine
Reading
Insulin
Endocytosis
Lysosomes
Membrane Proteins
trans-Golgi Network
Secretory Pathway
Endosomes
Golgi Apparatus
Cell membranes
Viperidae
Tail
Cell Membrane

Cite this

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title = "Distinct reading of different structural determinants modulates the dileucine-mediated transport steps of the lysosomal membrane protein LIMPII and the insulin-sensitive glucose transporter GLUT4",
abstract = "Leucine-based motifs mediate the sorting of membrane proteins at such cellular sites as the trans-Golgi network, endosomes, and plasma membrane. A Leu paired with a second Leu, He, or Met, while itself lacking the ability to mediate transport, is the key structural feature in these motifs, Here we have studied the structural differences between the leucine-based motifs contained in the COOH tails of LIMPII and GLUT4, two membrane proteins that are transported through the secretory pathway and are targeted to lysosomes (1-3) and to a perinuclear compartment adjacent to the Golgi complex (4), respectively. LIMPII and GLUT4 display negatively (Asp(470)/Glu(471)) and positively (Arg(484)/Ar-485) charged residues, respectively, at positions -4 and -5 upstream from the critical Leu residue. The change in the charge sign of residues -4 and -5 results in missorting of LIMPII and GLUT4. We note that the acidic Glu residue at position -4 is critical for efficient intracellular sorting of LIMPII to lysosomes, but is dispensable for its surface internalization by endocytosis. Efficient intracellular sorting and endocytosis of GLUT4 require an Arg pair between positions -4 and -7. These results are consistent with the existence of distinct leucine-based motifs and provide evidence of their different readings at different cellular sites.",
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TY - JOUR

T1 - Distinct reading of different structural determinants modulates the dileucine-mediated transport steps of the lysosomal membrane protein LIMPII and the insulin-sensitive glucose transporter GLUT4

AU - Sandoval, I V

AU - Martinez-Arca, S

AU - Valdueza, J

AU - Palacios, S

AU - Holman, G D

N1 - ID number: ISI:000166039500014

PY - 2000

Y1 - 2000

N2 - Leucine-based motifs mediate the sorting of membrane proteins at such cellular sites as the trans-Golgi network, endosomes, and plasma membrane. A Leu paired with a second Leu, He, or Met, while itself lacking the ability to mediate transport, is the key structural feature in these motifs, Here we have studied the structural differences between the leucine-based motifs contained in the COOH tails of LIMPII and GLUT4, two membrane proteins that are transported through the secretory pathway and are targeted to lysosomes (1-3) and to a perinuclear compartment adjacent to the Golgi complex (4), respectively. LIMPII and GLUT4 display negatively (Asp(470)/Glu(471)) and positively (Arg(484)/Ar-485) charged residues, respectively, at positions -4 and -5 upstream from the critical Leu residue. The change in the charge sign of residues -4 and -5 results in missorting of LIMPII and GLUT4. We note that the acidic Glu residue at position -4 is critical for efficient intracellular sorting of LIMPII to lysosomes, but is dispensable for its surface internalization by endocytosis. Efficient intracellular sorting and endocytosis of GLUT4 require an Arg pair between positions -4 and -7. These results are consistent with the existence of distinct leucine-based motifs and provide evidence of their different readings at different cellular sites.

AB - Leucine-based motifs mediate the sorting of membrane proteins at such cellular sites as the trans-Golgi network, endosomes, and plasma membrane. A Leu paired with a second Leu, He, or Met, while itself lacking the ability to mediate transport, is the key structural feature in these motifs, Here we have studied the structural differences between the leucine-based motifs contained in the COOH tails of LIMPII and GLUT4, two membrane proteins that are transported through the secretory pathway and are targeted to lysosomes (1-3) and to a perinuclear compartment adjacent to the Golgi complex (4), respectively. LIMPII and GLUT4 display negatively (Asp(470)/Glu(471)) and positively (Arg(484)/Ar-485) charged residues, respectively, at positions -4 and -5 upstream from the critical Leu residue. The change in the charge sign of residues -4 and -5 results in missorting of LIMPII and GLUT4. We note that the acidic Glu residue at position -4 is critical for efficient intracellular sorting of LIMPII to lysosomes, but is dispensable for its surface internalization by endocytosis. Efficient intracellular sorting and endocytosis of GLUT4 require an Arg pair between positions -4 and -7. These results are consistent with the existence of distinct leucine-based motifs and provide evidence of their different readings at different cellular sites.

M3 - Article

VL - 275

SP - 39874

EP - 39885

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

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