Comprehensive Characterization of the Complex lola Locus Reveals a Novel Role in the Octopaminergic Pathway via Tyramine Beta-Hydroxylase Regulation.

Détails

ID Serval
serval:BIB_C45AE4C60405
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Comprehensive Characterization of the Complex lola Locus Reveals a Novel Role in the Octopaminergic Pathway via Tyramine Beta-Hydroxylase Regulation.
Périodique
Cell reports
Auteur(s)
Dinges N., Morin V., Kreim N., Southall T.D., Roignant J.Y.
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
05/12/2017
Peer-reviewed
Oui
Volume
21
Numéro
10
Pages
2911-2925
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Longitudinals lacking (lola) is one of the most complex genes in Drosophila melanogaster, encoding up to 20 protein isoforms that include key transcription factors involved in axonal pathfinding and neural reprogramming. Most previous studies have employed loss-of-function alleles that disrupt lola common exons, making it difficult to delineate isoform-specific functions. To overcome this issue, we have generated isoform-specific mutants for all isoforms using CRISPR/Cas9. This enabled us to study specific isoforms with respect to previously characterized roles for Lola and to demonstrate a specific function for one variant in axon guidance via activation of the microtubule-associated factor Futsch. Importantly, we also reveal a role for a second variant in preventing neurodegeneration via the positive regulation of a key enzyme of the octopaminergic pathway. Thus, our comprehensive study expands the functional repertoire of Lola functions, and it adds insights into the regulatory control of neurotransmitter expression in vivo.
Mots-clé
Animals, Blotting, Western, Drosophila, Drosophila Proteins/metabolism, Drosophila melanogaster, In Situ Hybridization, Mixed Function Oxygenases/metabolism, Octopamine/metabolism, Protein Isoforms/metabolism, Transcription Factors/metabolism, CRISPR/Cas9, Futsch, Lola, Tyramine beta-hydroxylase, axon guidance, isoforms, octopaminergic neurons, splicing
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/10/2019 13:43
Dernière modification de la notice
29/10/2019 7:26
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