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Extracellular interaction between Neurotrophic factor-α1 and HTR1E serotonin receptor promotes cell survival

Sharma, Vinay Kumar and Xuyu, Yang and Sanchez, Daniel-Saiz and Kim, Soo-Kyung and Goddard, William A., III and Loh, Y. Peng (2020) Extracellular interaction between Neurotrophic factor-α1 and HTR1E serotonin receptor promotes cell survival. FASEB Journal, 34 (S1). p. 1. ISSN 0892-6638. https://resolver.caltech.edu/CaltechAUTHORS:20201009-133620451

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Abstract

Neurotrophic factor α1 (NFα1), classically known as carboxypeptidase E (CPE) has a non‐enzymatic role in the survival of neurons and cancer cells via binding to a putative receptor. We have identified 5‐Hydroxy tryptamine receptor 1E (HTR1E), a serotonin receptor with unknown function, as a binding partner that interacts with NFα1/CPE extracellularly to mediate cell survival. Co‐immunoprecipitation using a human LN18 cells and pull‐down assay with NFα1/CPE and HTR1E expressed in HEK293 cells confirmed interaction of these two molecules. ¹²⁵I NFα1/CPE binding studies demonstrated saturable, high affinity binding to HTR1E. Molecular docking studies revealed the surface interaction between NFa1/CPE and HTR1E via 3 salt bridges, further stabilized by hydrogen bonding. We also found that HTR1E was able to activate ERK/CREB signaling upon treatment with NFα1/CPE. Pretreatment of HTR1E stable cells with NFα1/CPE followed by H₂O₂‐induced oxidative stress prevented a decrease in pro‐survival protein BCL2 and reduced cytotoxicity. SiRNA knock‐down of HTR1E in U118 glioblastoma cells resulted in significant inhibition of these cancer cells survival. Immunocytochemical analysis of human hippocampus indicated co‐expression of HTR1E with NFα1/CPE in CA1‐3 and dentate gyrus, and cellular co‐localization at the cell membrane in CA3 neurons. This study has uncovered a novel role for HTR1E as a binding partner for NFα1/CPE, and their interaction activates the ERK‐CREB‐BCL2 pathway to promote cell survival.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1096/fasebj.2020.34.s1.01952DOIArticle
ORCID:
AuthorORCID
Kim, Soo-Kyung0000-0002-4498-5441
Goddard, William A., III0000-0003-0097-5716
Additional Information:© 2020 FASEB. Issue Online: 16 April 2020. Support or Funding Information: Division of intramural research, NICHD, NIH, Bethesda, MD, USA
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Funding AgencyGrant Number
NIHUNSPECIFIED
Issue or Number:S1
Record Number:CaltechAUTHORS:20201009-133620451
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201009-133620451
Official Citation:Sharma, V.K., Xuyu, Y., Sanchez, D., Kim, S., Goddard, W.A., III and Loh, Y.P. (2020), Extracellular interaction between Neurotrophic factor‐α1 and HTR1E serotonin receptor promotes cell survival. The FASEB Journal, 34: 1-1. doi:10.1096/fasebj.2020.34.s1.01952
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105971
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:09 Oct 2020 20:43
Last Modified:09 Oct 2020 20:43

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