Abstract: Uncovering the Role of MK-STYX in Neuronal Development

In recent years, neurological diseases like Alzheimer’s, ALS, Parkinson’s, and dementia have become much more prevalent. Yet, the mechanism and development of such diseases largely remain enigmatic, and treatment is generally limited to supportive care. Neurodegenerative diseases generally involve a disruption in communication between neurons, whether by cell death or by fewer connections with other neurons (Gao and Hong 2008). My research centers on MK-STYX (mitogen-activated protein kinase phosphoserine/threonine/tyrosine-binding protein), a protein implicated in neuronal development. MK-STYX belongs to a group of proteins called pseudophosphatases, which lack catalytic activity but have homology to enzymes that dephosphorylate proteins, phosphatases (Hinton et al 2010). Though MK-STYX is catalytically inactive, it still plays a role in many cell signaling pathways, including cellular stress response, apoptosis, and neuronal development (Flowers et al 2014, Hinton et al 2010, Niemi et al 2011).

My research in Dr. Hinton’s lab this summer will focus on which protein domain of MK-STYX causes morphological effects in primary neurons. Previous work found that MK-STYX induces an increase in the number of neurite outgrowths in neuron-like cells and that when MK-STYX is not present in those cells, there are no neurite extensions (Flowers et al 2014). Further studies found that MK-STYX also changes the shape of primary rat neurons, increasing the number of neurites and causing the axon to be visibly indistinguishable from other neurites (Banks et al 2017). MK-STYX has two protein domains, the DSP (dual specificity) and the CH2 (Rhodanese) domain (Niemi et al 2011). Through my research this summer, I will determine which protein domain of MK-STYX causes such effects in primary neurons. Identifying which domain causes these neuronal effects will help begin to uncover how, exactly, MK-STYX affects primary neuron development. This understanding could be used to halt and possibly even reverse the progression of neurodegenerative diseases.