Netrin-3-peptides Are Chemorepellents and Mitotic Inhibitors in Tetrahymena thermophila

Authors

Bethany C. Khol, Cedarville UniversityFollow
Katelyn Malik, Cedarville UniversityFollow
Kenneth W. Ward, Cedarville UniversityFollow
Matthew S. Merical, Cedarville UniversityFollow
Lois Parks, Cedarville UniversityFollow
Stephanie J. Hermann, Cedarville UniversityFollow
David Paulding, Cedarville UniversityFollow
Heather G. Kuruvilla, Cedarville UniversityFollow

ORCID

http://orcid.org/0000-0002-9386-9615

Document Type

Article

Publication Date

2018

Journal Title

Current Topics in Peptide & Protein Research

Volume

19

First Page

63

Last Page

73

Abstract

Netrins are a family of guidance proteins involved in developmental signaling as well as maintenance of homeostasis within the adult organism. Netrin-1 is the best characterized of all the netrins and has been linked to cancer, apoptosis, angiogenesis, and immune signaling. However, much less is known about netrin-3, especially its roles outside of development. In this study, we performed behavioral assays that demonstrated the chemorepellent effect of netrin-3-peptides on Tetrahymena thermophila. Our pharmacological inhibition assays showed that signaling is dependent on calcium and serine/threonine kinases. We also observed that exposing cells to netrin-3-peptides for two days caused a significant decrease in the mitotic rate. Inhibition of mitosis was rescued by adding calcium chelators or a serine/threonine kinase inhibitor to the culture media alongside the netrin-3-peptides. We also used immunofluorescence and enzyme-linked immunosorbent assay (ELISA) assays to determine that Tetrahymena secrete a netrin-3-like protein, suggesting a physiological role for a netrin-3-like signal in keeping cell populations from depleting their resources too rapidly. Finally, we contrasted signaling data from our studies with netrin-3-peptides to our data from our previous studies with netrin-1-peptide, showing that the two peptides use different signaling pathways, resulting in dissimilar physiological consequences for the organism.

Keywords

Netrin-3, netrin-1, chemorepellent, serine/threonine kinase, mitosis

Recommended Citation

Khol, Bethany C.; Malik, Katelyn; Ward, Kenneth W.; Merical, Matthew S.; Parks, Lois; Hermann, Stephanie J.; Paulding, David; and Kuruvilla, Heather G., "Netrin-3-peptides Are Chemorepellents and Mitotic Inhibitors in Tetrahymena thermophila" (2018). Science and Mathematics Faculty Publications. 370.
https://digitalcommons.cedarville.edu/science_and_mathematics_publications/370

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.