Dyneins, autophagy, aggregation and neurodegeneration.
We recently showed that the dynein motor machinery plays a role in the delivery of autophagosome contents to lysosomes, in the process of autophagosome-lysosome fusion. This may explain a number of important previous observations, including why intracellular aggregates form in mice with dynein mutations that have motor neuron-like disease. These studies highlight the importance of dyneins and autophagy in the clearance of aggregate-prone proteins in general, and also in the specific case of Huntington's disease. Since many common neurodegenerative diseases are associated with intracellular aggregate formation but the causative variants are unknown, it may be worth considering the possibility of genetic lesions affecting autophagy as contributing factors in such disorders. The importance of dyneins in autophagosome-lysosome fusion provides new insights for the microtubule dependency of autophagy. In this Addendum, we review our findings in the contexts of autophagy and neurodegeneration and consider some of the questions raised.
Rubinsztein
David C
DC
Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Cambridge, UK. dcr1000@hermes.cam.ac.uk
Ravikumar
Brinda
B
Acevedo-Arozena
Abraham
A
Imarisio
Sara
S
O'Kane
Cahir J
CJ
Brown
Steve D M
SD
D000818:Animals; D001343:Autophagy; D004398:Dyneins / Q000235:genetics / Q000502:physiology*; D006816:Huntington Disease / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009410:Nerve Degeneration / Q000473:pathology*; D010588:Phagosomes / Q000378:metabolism; D011485:Protein Binding
D004398:Dyneins