Authors:	Kilo, Lukas
Title:	Redundant, exclusive, and cooperative functions of alternative exons in Drosophila Cav2 channels
Online publication date:	7-Jul-2022
Year of first publication:	2022
Language:	english
Abstract:	The diversity of voltage gated calcium channel (VGCC) functions greatly outnumbers the count of voltage gated calcium channel genes. One of the ways to increase VGCC functional diversity is alternative splicing. In this thesis I could show for the Drosophila VGCC cacophony, a homolog to the vertebrate Cav2 calcium channel family, that functional diversity is indeed linked to alternative splicing. By using CRISPR/Cas for exon excision as well as electrophysiological methods, confocal microscopy, and behavioral assays, both isoform-specific properties and degenerate functions of exon dependent isoform subsets could be identified. Two alternative exon pairs encoding part of the voltage sensor or accessory subunit binding sites, respectively, were investigated. Differences in isoform localization as well as channel kinetics suggest a division of labor in some parts of the nervous system. Indeed, some of the isoforms fulfill essential functions with behavioral relevance, while others function in a degenerate manner. Although, whether these degenerate ones also exert unique functions under specific conditions remains to be determined. In addition to this, a novel collaborative interaction between two isoforms of the same gene could be discovered. Specifically, lethality resulting from the deletion of one essential isoform and behavioral impairments resulting from the deletion from the other alternative isoform are both fully rescued in trans heterozygous flies carrying both deletions. Both alternative exons have rather similar channel properties but different global and subcellular localizations. They are both required in concert throughout the nervous system for survival and normal motor behavior.
DDC:	500 Naturwissenschaften 500 Natural sciences and mathematics 570 Biowissenschaften 570 Life sciences 590 Tiere (Zoologie) 590 Zoological sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 10 Biologie
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7162
URN:	urn:nbn:de:hebis:77-openscience-6d45d5b8-9ca1-4b89-bea7-5df7855f9a3e1
Version:	Original work
Publication type:	Dissertation
License:	In Copyright
Information on rights of use:	http://rightsstatements.org/vocab/InC/1.0/
Extent:	VII, 130 Seiten, Illustrationen
Appears in collections:	JGU-Publikationen