Functional analysis of CASK transcript variants expressed in human brain

The calcium-/calmodulin dependent serine protein kinase (CASK) belongs to the membrane-associated guanylate kinases (MAGUK) family of proteins. It fulfils several different cellular functions, ranging from acting as a scaffold protein to transcription control, as well as regulation of receptor sorti...

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Bibliographic Details
Published in:PloS one 2021-06, Vol.16 (6), p.e0253223-e0253223
Main Authors: Tibbe, Debora, Pan, Yingzhou Edward, Reißner, Carsten, Harms, Frederike L, Kreienkamp, Hans-Jürgen
Format: Article
Language:English
Subjects:
Alternative splicing
Analysis
Barrels
Biology and life sciences
Brain
Cell adhesion & migration
Cloning
Coding
Cytoskeleton
Ethics
Functional analysis
Gene expression
Genetic aspects
Genomes
Ion channels
Isoforms
Kinases
Kinesin
Localization
Molecular motors
Neural coding
Postsynaptic density
Protein kinases
Protein-protein interactions
Proteins
Research and Analysis Methods
Scaffolds
Signal transduction
Transcription
Transcription factors
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Summary:The calcium-/calmodulin dependent serine protein kinase (CASK) belongs to the membrane-associated guanylate kinases (MAGUK) family of proteins. It fulfils several different cellular functions, ranging from acting as a scaffold protein to transcription control, as well as regulation of receptor sorting. CASK functions depend on the interaction with a variety of partners, for example neurexin, liprin-[alpha], Tbr1 and SAP97. So far, it is uncertain how these seemingly unrelated interactions and resulting functions of CASK are regulated. Here, we show that alternative splicing of CASK can guide the binding affinity of CASK isoforms to distinct interaction partners. We report seven different variants of CASK expressed in the fetal human brain. Four out of these variants are not present in the NCBI GenBank database as known human variants. Functional analyses showed that alternative splicing affected the affinities of CASK variants for several of the tested interaction partners. Thus, we observed a clear correlation of the presence of one splice insert with poor binding of CASK to SAP97, supported by molecular modelling. The alternative splicing and distinct properties of CASK variants in terms of protein-protein interaction should be taken into consideration for future studies.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0253223