Science
95 A Novel Organelle of the Synapse
Gareema Dhiman
Faculty Mentor: Erik Jorgensen (School of Biological Sciences, University of Utah)
During neurotransmission, neurons constantly fuse and recycle synaptic vesicles from the presynaptic membrane. Like other organelles, synaptic vesicles and proteins must be removed when damaged or overused. Build-up of damaged proteins may underlie neurodegenerative diseases like Parkinson’s Disease. However, a pathway for removal of synaptic material is unknown. Common degradative pathways of neuronal cells include the autophagy, proteasome, and endo-lysosomal systems. Damage within any of these pathways leads to accumulation of waste at synapses. Members of the Jorgensen lab have recently discovered a new organelle in Caenorhabditis elegans called a surveillant. The lysosome-derived organelle is found to probe synaptic spaces and take up synaptic proteins and aggregates. Surveillant numbers doubled when stressed using a 34° C heat shock for 4 hours. Surveillants share important similarities to lysosomes; however, surveillants are transported to and from synapses, unlike lysosomes, which reside in the cell soma. To better understand the origins of surveillants, I aim to answer the question, what is the molecular composition of surveillants? To address this, we have tagged synaptic vesicle proteins as well as autophagy and lysosomal proteins with fluorescent proteins to measure if they colocalize with surveillants. Identifying whether colocalization occurs is important in uncovering what pathway surveillants are involved in and how they can be differentiated from other degradative organelles. This research is important for broadening our understanding of how neurons respond to severe stress, with relevance to human diseases such as stroke, Alzheimer’s, and Parkinson’s Disease.
A special thanks is also extended to my father, whose encouragement, support, and generosity has given me the strength and perseverance to pursue and achieve my goals.
Figure 1: Lysosomes (red) are contained in the cell body and axon initial segment (AIS) in a C. elegans neuronal cell. At the synapses waste often builds up (green) that can lead to neurodegenerative diseases if not effectively degraded.
Proteins destined for degradation in the lysosome are transported by organelles such as late endosomes or autophagosomes. This allows for proper sorting and recycling of cellular components at synapses (Yu, 2018). During macroautophagy (generally referred to as autophagy) a double membrane forms around damaged proteins or other small organelles to form an autophagosome (Figure 2) (Yu, 2018). The autophagosomes are transported back along the axon and eventually fuse with lysosomes. In addition to macroautphagy, damaged proteins and organelles as well as endocytic vesicles can be degraded through microautophagy, endosomal microautophagy, and chaperone-mediated autophagy. Another main degradative pathway is the proteasome/ubiquitin (Figure