Classical autophagy proteins LC3B and ATG4B facilitate melanosome movement on cytoskeletal tracks.
Autophagy
; 13(8): 1331-1347, 2017 Aug 03.
Article
em En
| MEDLINE
| ID: mdl-28598240
ABSTRACT
Macroautophagy/autophagy is a dynamic and inducible catabolic process that responds to a variety of hormonal and environmental cues. Recent studies highlight the interplay of this central pathway in a variety of pathophysiological diseases. Although defective autophagy is implicated in melanocyte proliferation and pigmentary disorders, the mechanistic relationship between the 2 pathways has not been elucidated. In this study, we show that autophagic proteins LC3B and ATG4B mediate melanosome trafficking on cytoskeletal tracks. While studying melanogenesis, we observed spatial segregation of LC3B-labeled melanosomes with preferential absence at the dendritic ends of melanocytes. This LC3B labeling of melanosomes did not impact the steady-state levels of these organelles but instead facilitated their intracellular positioning. Melanosomes primarily traverse on microtubule and actin cytoskeletal tracks and our studies reveal that LC3B enables the assembly of microtubule translocon complex. At the microtubule-actin crossover junction, ATG4B detaches LC3B from melanosomal membranes by enzymatic delipidation. Further, by live-imaging we show that melanosomes transferred to keratinocytes lack melanocyte-specific LC3B. Our study thus elucidates a new role for autophagy proteins in directing melanosome movement and reveal the unconventional use of these proteins in cellular trafficking pathways. Such crosstalk between the central cellular function and housekeeping pathway may be a crucial mechanism to balance melanocyte bioenergetics and homeostasis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Citoesqueleto
/
Cisteína Endopeptidases
/
Melanossomas
/
Proteínas Relacionadas à Autofagia
/
Proteínas Associadas aos Microtúbulos
/
Movimento
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article