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J. Biol. Chem., Vol. 275, Issue 51, 39874-39885, December 22, 2000
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From the 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, Ile, 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 (Asp470/Glu471) and positively
(Arg484/Arg485) charged residues, respectively,
at positions
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*
§,
,
,
, and
Centro de Biología Molecular
"Severo Ochoa," Consejo Superior de Investigaciones
Científicas, Facultad de Ciencias, Universidad
Autónoma de Madrid, Cantoblanco, Madrid 28049, Spain and the
¶ Department of Biochemistry, University of Bath, Claverton Down,
Bath BA2 7AY, United Kingdom
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.
*
This work was supported in part by Grant PB94-0035 from the
Comisión Interministerial para Ciencia y
Tecnología of the Spanish Government, Grant Exp 08.6/0017/1997
from the Comunidad de Madrid, and Grants BMHY-CT-96-0010 and
FMRX-CT-96-0018 from the EC Comisión (to I. V. S.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of a grant from the Medical Research Council (United Kingdom).
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