Scholars@Duke publication: Reversion mutation of cDNA CA8-204 minigene construct produces a truncated functional peptide that regulates calcium release in vitro and produces profound analgesia in vivo.

Reversion mutation of cDNA CA8-204 minigene construct produces a truncated functional peptide that regulates calcium release in vitro and produces profound analgesia in vivo.

Publication , Journal Article

Upadhyay, U; Zhuang, GZ; Diatchenko, L; Parisien, M; Kang, Y; Sarantopoulos, KD; Martin, ER; Smith, SB; Maixner, W; Levitt, RC

Published in: Mamm Genome

December 2020

Published version (DOI) Link to item

Intracellular calcium is critical in orchestrating neuronal excitability and analgesia. Carbonic anhydrase-8 (CA8) regulates intracellular calcium signaling through allosteric inhibition of neuronal inositol trisphosphate receptor 1 (ITPR1) to produce profound analgesia. Recently, we reported the "G" allele at rs6471859 represents cis-eQTL regulating alternative splicing of a 1697 bp transcript (CA8-204G) with a retained intron, alternative polyadenylation site and a new stop codon producing a functional 26 kDa peptide with an extended exon 3. In this study we show the reversion mutation (G to C) at rs6471859 within the CA8-204G expression vector also produced a stable 1697 bp transcript (CA8-204C) coding for a smaller peptide (~ 22 kDa) containing only the first three CA8 exons. Surprisingly, this peptide inhibited ITPR1 (pITPR1) activation, ITPR1-mediated calcium release in vitro; and produced profound analgesia in vivo. This is the first report showing CA8-204C codes for a functional peptide sufficient to regulate calcium signaling and produce profound analgesia.

Duke Scholars

Author Luda Diatchenko Anesthesiology

Author Shad Benjamin Smith Anesthesiology

Published In

Mamm Genome

DOI

10.1007/s00335-020-09848-y

EISSN

1432-1777

Publication Date

December 2020

Volume

Issue

9-12

Start / End Page

287 / 294

Location

United States

Related Subject Headings

Transduction, Genetic
Peptides
Pain
Mutation
Mice
Humans
Genetics & Heredity
Genetic Vectors
Gene Transfer Techniques
Dependovirus

Citation

APA

Chicago

ICMJE

MLA

NLM

Upadhyay, U., Zhuang, G. Z., Diatchenko, L., Parisien, M., Kang, Y., Sarantopoulos, K. D., … Levitt, R. C. (2020). Reversion mutation of cDNA CA8-204 minigene construct produces a truncated functional peptide that regulates calcium release in vitro and produces profound analgesia in vivo. Mamm Genome, 31(9–12), 287–294. https://doi.org/10.1007/s00335-020-09848-y

Upadhyay, Udita, Gerald Z. Zhuang, Luda Diatchenko, Marc Parisien, Yuan Kang, Konstantinos D. Sarantopoulos, Eden R. Martin, Shad B. Smith, William Maixner, and Roy C. Levitt. “Reversion mutation of cDNA CA8-204 minigene construct produces a truncated functional peptide that regulates calcium release in vitro and produces profound analgesia in vivo.” Mamm Genome 31, no. 9–12 (December 2020): 287–94. https://doi.org/10.1007/s00335-020-09848-y.

Upadhyay U, Zhuang GZ, Diatchenko L, Parisien M, Kang Y, Sarantopoulos KD, et al. Reversion mutation of cDNA CA8-204 minigene construct produces a truncated functional peptide that regulates calcium release in vitro and produces profound analgesia in vivo. Mamm Genome. 2020 Dec;31(9–12):287–94.

Upadhyay, Udita, et al. “Reversion mutation of cDNA CA8-204 minigene construct produces a truncated functional peptide that regulates calcium release in vitro and produces profound analgesia in vivo.” Mamm Genome, vol. 31, no. 9–12, Dec. 2020, pp. 287–94. Pubmed, doi:10.1007/s00335-020-09848-y.

Upadhyay U, Zhuang GZ, Diatchenko L, Parisien M, Kang Y, Sarantopoulos KD, Martin ER, Smith SB, Maixner W, Levitt RC. Reversion mutation of cDNA CA8-204 minigene construct produces a truncated functional peptide that regulates calcium release in vitro and produces profound analgesia in vivo. Mamm Genome. 2020 Dec;31(9–12):287–294.