THE EFFECTS OF AUTOPHAGIC PROTEINS ON FOCAL ACCUMULATIONS OF KINESIN MUTANTS IN DROSOPHILA AXONS
Physical and Biological Sciences
Saxton Lab
Many neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and Hereditary spastic paraplegia (HSP) are linked to axonal transport defects. Neurons are polarized cells; their site of biosynthesis is separated from the terminals by a long process known as the axon. Because of their highly elongated structure, the ability to efficiently move materials from one part of the cell to another is an important feature for neuronal survival. Thus, disruption to axonal transport can have detrimental effects on the neuron. One of the key proteins involved in transport is Kinesin-1. Kinesin-1 mutants in Drosophila show characteristics that closely mirror those seen in HSP. The axons of Kinesin-1 Drosophila mutants exhibit huge accumulations of organelles. The mechanism underlying the formation of these accumulations is unknown.
Our prediction is that specific organelles within these accumulations signal for a process called autophagy to remove them. If autophagy is degrading organelles within the accumulation, an increase in autophagy should lead to a decrease in accumulations. To test this hypothesis, we used Drosophila as a model for HSP and modified the degree of autophagy occurring in the cell by altering specific protein expression levels. Our results show that by increasing autophagy there is a decrease in accumulations. This leads to the conclusion that autophagy counteracts the degeneration of axons seen in diseases such as HSP.
