The CH2 Domain of Pseudophosphatase MK‐STYX Regulates Neurites in Neuronal Models

• Published in: The FASEB journal 2020-04, Vol.34 (S1), p.1-1
• Main Authors: Zhang, Ashley M., Reed, Kirstin M., Hinton, Shantá D.
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2020.34.s1.03792

Abstract only Pseudoenzymes are emerging as key regulators in signal transduction cascades. Pseudophosphatases have been implicated in diseases such as Alzheimer’s, cancer, metabolic disorder, and obesity, highlighting their importance in cellular processes. The unique catalytically inactive member of the mitogen‐activated protein kinase phosphatases (MKP) family, MK‐STYX (mitogen activated kinase phosphoserine/threonine/tyrosine binding protein), is a regulator in the stress response, apoptosis, and neuronal differentiation. We previously reported that MK‐STYX increases neurite outgrowths in PC‐12 cells through the RhoA signaling pathway and these MK‐STYX‐induced neurites have post‐synaptic and pre‐synaptic properties when stained with the classical axon and dendrite markers, Tau‐1 and MAP2 (microtubule‐associated protein 2) respectively. In primary neurons, MK‐STYX causes morphological changes, such as axons and dendrites being visibly indistinguishable. Thus, it is apparent that MK‐STYX has a role in neuronal differentiation. To investigate the molecular mechanism that MK‐STYX utilizes to cause neurite formation, PC‐12 cells expressing GFP‐tagged truncated versions of MK‐STYX rhodanese (cdc 25 homology; CH2) or dual specificity phosphatase (DSP) domain and stimulated with NGF were analyzed for neurite outgrowths. Cells expressing the CH2 domain formed a significant number of neurites, whereas cells expressing the DSP domain produced no neurites. Moreover, we expressed the active form of MK‐STYX and wild type MK‐STYX in N2A cells and stimulated them with retinoic acid. Similar to our previous report, we again saw an increase in neurite outgrowths in cells expressing wild‐type MK‐STYX. In addition, we replicated expression of the truncated versions of MK‐STYX in N2A cells. Again, we observed an increase of neurites in N2A cells expressing the CH2 domain. Taken together, these data provide evidence that MK‐STYX is a regulator in neurite formation, and that the CH2 domain is key for regulation in neurite differentiation while the DSP domain may be the accessory domain. It also highlights that this unique member of the MKP subfamily potentially has a major role in neuronal signaling.