| Description |
Cells require degradative pathways that assist in disposing of damaged proteins and organelles and recycling their contents. Proteins and membrane within the cell can be used several times before being degraded, but with more use, these components may become more suspectable to damage that interferes with their function. Damaged proteins are often marked for degradation by a ubiquitin tag, which allows degradative machinery to recognize the substrate and degrade it. However, organelles consist of membrane and several proteins that require more specialized forms of degradation, such as engulfment by or fusion with another organelle. Neurons are nonregenerative cells, making them particularly dependent on proper quality control. Neurons form synapses with other cells, creating a network of synaptic connections that are necessary to form and maintain memories. These synapses contain synaptic vesicles that regularly fuse to the plasma membrane, release their neurotransmitters, and are reinternalized. Failure to properly recycle subcellular components at synapses can result in the accumulation of aggregated proteins that initiate neurodegenerative diseases, like Parkinson's disease and Alzheimer's disease. Several degradative processes are involved in maintaining turnover of synaptic proteins and organelles to prevent neurodegenerative diseases, but the specific mechanisms are complex and not fully elucidated. One degradative pathway that is required for the establishment of synapses is autophagy. In autophagy, a large double-membraned organelle engulfs its cargo and is transported to the lysosome for degradation. In Chapter 2 of this dissertation, I investigate how synaptic activity influences autophagy in adult Caenorhabditis elegans. In Chapter 3, I begin to characterize how stress affects autophagy and ultimately discover a new lysosome-derived organelle at synapses. Together, these data contribute to better understanding how degradation occurs in the adult nervous system and what cellular processes need to be maintained to avoid neurodegenerative disease. |
