1 t dimers and test candidate explanations for
limping.
2 or the origin of kinesin step asymmetry and "
limping."
3 Enterovirus 71 also binds to
LIMP-
2 (also known as SCARB2) on the external surface of
4 ucocerbrosidase (GCase)) binding sequence to
LIMP-
2 (lysosomal integral membrane protein 2), the rece
5 Heterologous expression of
LIMP-
2 accelerated clearance of overexpressed alpha-synu
6 n at any of these decreases GCase binding to
LIMP-
2 and alters its pH-dependent binding as well as di
7 a similar affinity to that observed between
LIMP-
2 and beta-GCase.
8 ino acid, but the interactions of GCase with
LIMP-
2 are heavily influenced by Asp(399) and the di-iso
9 These data support a role for
LIMP-
2 as the mannose-6-phosphate-independent traffickin
10 Remarkably, we find that
LIMP-
2 bears P-Man9GlcNAc2 covalently attached to residu
11 l interface region within GC as critical for
LIMP-
2 binding and lysosomal transport.
12 e report structural results illuminating how
LIMP-
2 binds and releases beta-GCase according to change
13 LIMP-
2 deficiency is associated with neurological abnorm
14 a demonstrated that the crystal structure of
LIMP-
2 displays a hydrophobic three-helix bundle compose
15 LIMP-
2 expression also led to lysosomal transport of a b
16 Therefore, we suggest that manipulating
LIMP-
2 expression to increase lysosomal GC activity is a
17 In cellular uptake experiments,
LIMP-
2 facilitates transport of phospholipids into murin
18 basis and functional importance of a form of
LIMP-
2 for lipid trafficking.
19 Binding of these lipids alters
LIMP-
2 from functioning as a glucocerebrosidase-binding
20 o be responsible for controlling the exit of
LIMP-
2 from the Golgi.
21 Variants in the
LIMP-
2 gene cause action myoclonus-renal failure syndrom
22 The integral membrane protein
LIMP-
2 has been a paradigm for mannose 6-phosphate recep
23 Based on these findings, we generated a
LIMP-
2 helix 5-derived peptide that precipitated and act
24 Given the importance of GC and
LIMP-
2 in disease pathogenesis, we studied their interac
25 olgi compartment, leading to accumulation of
LIMP-
2 in enlarged endosomal vesicles.
26 Reconstitution of
LIMP-
2 in LIMP-2-deficient fibroblasts led to a rescue o
27 hosphate in the Golgi caused accumulation of
LIMP-
2 in this compartment, and PI4KIIIbeta was found to
28 imaging microscopy, we also demonstrate that
LIMP-
2 interacts with MPR in living cells.
29 that the lysosomal integral membrane protein
LIMP-
2 is a specific binding partner of beta-glucocerebr
30 The binding to
LIMP-
2 is not dependent upon a single amino acid, but th
31 n surviving DA neurons of human PD midbrain,
LIMP-
2 levels were increased, probably to compensate for
32 via a histidine trigger, and suggesting that
LIMP-
2 localizes the ceramide portion of the substrate a
33 Here we report a crystal structure of a
LIMP-
2 luminal domain dimer with bound cholesterol and p
34 g between monomeric and dimeric forms allows
LIMP-
2 to engage distinct binding partners, a mechanism
35 resulted in their rapid degradation, whereas
Limp-
2 was relatively stable in the lysosome in the abse
36 lysosomal integral membrane protein type-2 (
LIMP-
2) plays a pivotal role in the delivery of beta-glu
37 lysosomal integral membrane protein type-2 (
LIMP-
2), we studied alpha-synuclein metabolism in LIMP-2
38 lysosomal integral membrane protein type 2 (
LIMP-
2).
39 These results revise the accepted view of
LIMP-
2-beta-GCase lysosomal targeting.
40 In
LIMP-
2-deficient brains a significant reduction in GC ac
41 Reconstitution of LIMP-2 in
LIMP-
2-deficient fibroblasts led to a rescue of beta-glu
42 evels were significantly higher in sera from
LIMP-
2-deficient mice compared to wild-type.
43 2), we studied alpha-synuclein metabolism in
LIMP-
2-deficient mice.
44 nd protein levels were severely decreased in
LIMP-
2-deficient mouse tissues.
45 uced alpha-synuclein levels, suggesting that
LIMP-
2-derived peptides can be used to activate endogeno
46 enger receptor proteins highly homologous to
LIMP-
2.
47 s interaction with the transmembrane protein
LIMP-
2.
48 iple steps in the trafficking pathway of the
LIMP-
2/GBA complex.
49 the medium, which was attenuated by limiting
LIMP-
2/GBA exit from the Golgi by PI4KIIIbeta inhibitors
50 data also provide a structural model of the
LIMP-
2/GC complex that will facilitate the development o
51 However, the
LIMP-
2/SCARB2 binding sequences for enterovirus 71 and G
52 1 and GCase are not similar, indicating that
LIMP-
2/SCARB2 may have multiple or overlapping binding s
53 Lysosomal integral membrane protein-2 (
LIMP-
2/SCARB2) contributes to endosomal and lysosomal fu
54 n sequential steps, causing these motors to "
limp"
along the microtubule.
55 itioning were combined, the rats developed a
limp and a tilted posture that correlated in direction a
56 The bulk elastic properties of
limp and aging cellular solids are calculated for model
57 in stalk stiffness, ruling out models where
limping arises from an asymmetry in torsional strain.
58 stigation of young children who present with
limping as their only or predominant symptom.
59 Defect-only rabbits
limped at all times.
60 The mechanics of an aged,
limp beam is calculated, thus offering a practical proce
61 Limping behavior implies that the molecular rearrangemen
62 how that the experimentally observed kinesin
limping can be explained in our model by the variation o
63 GFP tagging of
LIMP caused a limping defect during movement with reduce
64 GFP tagging of LIMP caused a
limping defect during movement with reduced speed and tr
65 tructs with short stalks have been found to "
limp",
i.e., exhibit alternation in the dwell times of s
66 ctivity of the glycine motif-deficient SR-BI/
LIMP II chimera was low but could be increased by introd
67 The rate of lipid uptake mediated by SR-BI/
LIMP II chimeras was proportional to the extent of recep
68 acking (lysosomal integral membrane protein (
LIMP)
II) this glycine motif (chimeras).
69 LCMV was greatly enhanced by addition of the
LIMP-
II tail.
70 pe was almost abolished when attached to the
LIMP-
II tail.
71 l of lysosomal integral membrane protein-II (
LIMP-
II).
72 Limping implies that kinesin molecules strictly alternat
73 ne of the most common causes of hip pain and
limp in young children.
74 elatively common conditions that can produce
limping in children 1-6 yr old.
75 LIMP is an essential motility and invasion factor necess
76 Transcribed in gametocytes,
LIMP is translated in the ookinete from maternal mRNA, a
77 The absence of
LIMP reduces initial mosquito infection by 50%, impedes
78 chanism by which such rearrangements lead to
limping remains unsolved.
79 stalk region near the heads had no effect on
limping,
ruling out possible stalk misregistration durin
80 fusion protein and five out of 10 developed
limp tails.
81 integral membrane proteins (termed Lamps and
Limps)
that are extensively glycosylated with asparagine
82 Here, we identify the Plasmodium protein
LIMP (
the name refers to a gliding phenotype in the spor
83 However,
limping was enhanced by perturbations that increased the
84 Limping was equally unaffected by mutations that produce