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Characterizing the Alternative Splicing Dynamics of Ca v 1.3, a Calcium Ion Channel Involved in Autism Spectrum Disorder
Author(s) -
Mirkovic Jovan,
Sabzanov Samuel,
Wang Ruizhi,
Hossain Faruk,
Ruggiu Matteo
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.459.11
Subject(s) - alternative splicing , gene isoform , voltage dependent calcium channel , calcium channel , biology , ion channel , g alpha subunit , transmembrane domain , exon , microbiology and biotechnology , calcium , protein subunit , genetics , chemistry , gene , receptor , organic chemistry
Voltage‐gated calcium channels move calcium ions across cellular membranes in response to action potential stimuli, which mediate processes including cellular signaling, neurotransmitter discharge, muscle contraction, and gene expression. They are multimer proteins composed of alpha‐1, beta, alpha‐2/delta, and gamma subunits. Variety in calcium channels is afforded by different subtypes of alpha‐1, including the A, B, C, D, E, and S isoforms. Ca v 1.3 is a member of the L‐type calcium channels and is categorized in the high‐voltage activated family. It employs the alpha‐1 subunit encoded by the CACNA1D gene. The alpha‐1 subunit forms four homologous repeat domains, each consisting of six transmembrane helical segments. Cacna1d knock out mice suffer from bradycardia and congenital deafness, testifying to the significance of the alpha‐1 subunit in the sinoatrial node and in auditory hair cells. Naturally occurring missense mutations in alternatively spliced regions of CACNA1D , such as the mutually exclusive exons 8a and 8b encoding part of the sixth transmembrane segment of domain I, have been reported to be gain‐of‐function mutations, which cause aldosterone‐producing adenomas, aldosteronism, seizures, and autism spectrum disorder, highlighting the importance of alternative splicing for Ca v 1.3 function. Although the diseases derived from CACNA1D mutations have been characterized, the splicing dynamics of the CACNA1D pre‐mRNA that gives rise to the different alpha‐1 isoforms is not well understood. Here, we describe the alternatively spliced isoforms of Cacna1d and their distribution in mouse tissues. Support or Funding Information National Institute of General Medical Sciences Grant 1R15GM119099‐01 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .