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The CH2 Domain of Pseudophosphatase MK‐STYX Regulates Neurite Outgrowth
Author(s) -
Reed Kirstin,
Zhang Ashley,
Whitehurst Wesley,
Hinton Shantá D.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.645.2
Subject(s) - neurite , biology , microbiology and biotechnology , signal transduction , neuron , rhoa , hippocampal formation , neuroscience , biochemistry , in vitro
Pseudoenzymes are emerging as key regulators in signal transduction cascades. More specifically, pseudophosphatases have been implicated in diseases such as Alzheimer's disease, 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. Recently, we found that MK‐STYX overexpressing cells produce more growth cones than control cells. Furthermore, immunoblots show that MK‐STYX overexpressing cells have increased actin expression, which is sustained in the presence or absence of nerve growth factor. 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. Furthermore, a dopamine assay demonstrated that MK‐STYX‐induced neurites are dopaminergic. In primary neurons, MK‐STYX causes morphological changes, such as axons and dendrites being visibly indistinguishable. MK‐STYX also elicits a significant increase in the number of neurites per neuron in hippocampal primary neurons. 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 only the DSP domain produced no neurites. Furthermore, cells expressing the DSP domain of MK‐STYX had significantly fewer neurites compared to cells expressing wild‐type MK‐STYX. Taken together, these data provide evidence that MK‐STYX is a regulator in neurite formation and that the CH2 domain is key for regulating 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. Support or Funding Information Grace Blank Award; The Mary E. Ferguson Memorial Research Grant This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .