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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Autores principales:	Debora Tibbe, Yingzhou Edward Pan, Carsten Reißner, Frederike L Harms, Hans-Jürgen Kreienkamp
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3a47d9e540c1444e84b644b38e144af3
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spelling	oai:doaj.org-article:3a47d9e540c1444e84b644b38e144af32021-12-02T20:10:34ZFunctional analysis of CASK transcript variants expressed in human brain.1932-620310.1371/journal.pone.0253223https://doaj.org/article/3a47d9e540c1444e84b644b38e144af32021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253223https://doaj.org/toc/1932-6203The 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-α, 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.Debora TibbeYingzhou Edward PanCarsten ReißnerFrederike L HarmsHans-Jürgen KreienkampPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0253223 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Debora Tibbe Yingzhou Edward Pan Carsten Reißner Frederike L Harms Hans-Jürgen Kreienkamp Functional analysis of CASK transcript variants expressed in human brain.
description	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-α, 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.
format	article
author	Debora Tibbe Yingzhou Edward Pan Carsten Reißner Frederike L Harms Hans-Jürgen Kreienkamp
author_facet	Debora Tibbe Yingzhou Edward Pan Carsten Reißner Frederike L Harms Hans-Jürgen Kreienkamp
author_sort	Debora Tibbe
title	Functional analysis of CASK transcript variants expressed in human brain.
title_short	Functional analysis of CASK transcript variants expressed in human brain.
title_full	Functional analysis of CASK transcript variants expressed in human brain.
title_fullStr	Functional analysis of CASK transcript variants expressed in human brain.
title_full_unstemmed	Functional analysis of CASK transcript variants expressed in human brain.
title_sort	functional analysis of cask transcript variants expressed in human brain.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/3a47d9e540c1444e84b644b38e144af3
work_keys_str_mv	AT deboratibbe functionalanalysisofcasktranscriptvariantsexpressedinhumanbrain AT yingzhouedwardpan functionalanalysisofcasktranscriptvariantsexpressedinhumanbrain AT carstenreißner functionalanalysisofcasktranscriptvariantsexpressedinhumanbrain AT frederikelharms functionalanalysisofcasktranscriptvariantsexpressedinhumanbrain AT hansjurgenkreienkamp functionalanalysisofcasktranscriptvariantsexpressedinhumanbrain
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Functional analysis of CASK transcript variants expressed in human brain.

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