Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis.
J Cell Biol
; 210(4): 595-611, 2015 Aug 17.
Article
em En
| MEDLINE
| ID: mdl-26261180
ABSTRACT
The degradation of phagosomes, derived from the ingestion of photoreceptor outer segment (POS) disk membranes, is a major role of the retinal pigment epithelium (RPE). Here, POS phagosomes were observed to associate with myosin-7a, and then kinesin-1, as they moved from the apical region of the RPE. Live-cell imaging showed that the phagosomes moved bidirectionally along microtubules in RPE cells, with kinesin-1 light chain 1 (KLC1) remaining associated in both directions and during pauses. Lack of KLC1 did not inhibit phagosome speed, but run length was decreased, and phagosome localization and degradation were impaired. In old mice, lack of KLC1 resulted in RPE pathogenesis that was strikingly comparable to aspects of age-related macular degeneration (AMD), with an excessive accumulation of RPE and sub-RPE deposits, as well as oxidative and inflammatory stress responses. These results elucidate mechanisms of POS phagosome transport in relation to degradation, and demonstrate that defective microtubule motor transport in the RPE leads to phenotypes associated with AMD.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Fagossomos
/
Epitélio Pigmentado da Retina
/
Degeneração Macular
/
Proteínas Associadas aos Microtúbulos
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2015
Tipo de documento:
Article