| RRC ID |
27
|
| 著者 |
Koike M, Shibata M, Waguri S, Yoshimura K, Tanida I, Kominami E, Gotow T, Peters C, von Figura K, Mizushima N, Saftig P, Uchiyama Y.
|
| タイトル |
Participation of autophagy in storage of lysosomes in neurons from mouse models of neuronal ceroid-lipofuscinoses (Batten disease).
|
| ジャーナル |
Am J Pathol
|
| Abstract |
In cathepsin D-deficient (CD-/-) and cathepsins B and L double-deficient (CB-/-CL-/-) mice, abnormal vacuolar structures accumulate in neurons of the brains. Many of these structures resemble autophagosomes in which part of the cytoplasm is retained but their precise nature and biogenesis remain unknown. We show here how autophagy contributes to the accumulation of these vacuolar structures in neurons deficient in cathepsin D or both cathepsins B and L by demonstrating an increased conversion of the molecular form of MAP1-LC3 for autophagosome formation from the cytosolic form (LC3-I) to the membrane-bound form (LC3-II). In both CD-/- and CB-/-CL-/- mouse brains, the membrane-bound LC3-II form predominated whereas MAP1-LC3 signals accumulated in granular structures located in neuronal perikarya and axons of these mutant brains and were localized to the membranes of autophagosomes, evidenced by immunofluorescence microscopy and freeze-fracture-replica immunoelectron microscopy. Moreover, as in CD-/- neurons, autofluorescence and subunit c of mitochondrial ATP synthase accumulated in CB-/-CL-/- neurons. This suggests that not only CD-/- but also CB-/-CL-/- mice could be useful animal models for neuronal ceroid-lipofuscinosis/Batten disease. These data strongly argue for a major involvement of autophagy in the pathogenesis of Batten disease/lysosomal storage disorders.
|
| 巻・号 |
167(6)
|
| ページ |
1713-28
|
| 公開日 |
2005-12-1
|
| DOI |
10.1016/S0002-9440(10)61253-9
|
| PII |
S0002-9440(10)61253-9
|
| PMID |
16314482
|
| PMC |
PMC1613187
|
| MeSH |
Animals
Autophagy
Cathepsin B / deficiency
Cathepsin B / genetics
Cathepsin D / deficiency
Cathepsin D / genetics
Disease Models, Animal
Freeze Fracturing
Genetic Carrier Screening
Lysosomes / pathology*
Mice
Mice, Knockout
Neuronal Ceroid-Lipofuscinoses / genetics
Neuronal Ceroid-Lipofuscinoses / pathology*
Neurons / pathology*
Neurons / ultrastructure
Reverse Transcriptase Polymerase Chain Reaction
|
| IF |
3.491
|
| 引用数 |
244
|
|
WOS 分野
|
PATHOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC00806 |
