Functional analysis of CASK transcript variants expressed in human brain.
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Functional analysis of CASK transcript variants expressed in human brain. / Tibbe, Debora Rabea Uta; Pan, Yingzhou Edward; Reißner, Carsten; Harms, Frederike Leonie; Kreienkamp, Hans-Jürgen.
In: PLOS ONE, Vol. 16, No. 6, e0253223, 2021, p. e0253223.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Functional analysis of CASK transcript variants expressed in human brain.
AU - Tibbe, Debora Rabea Uta
AU - Pan, Yingzhou Edward
AU - Reißner, Carsten
AU - Harms, Frederike Leonie
AU - Kreienkamp, Hans-Jürgen
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
UR - https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253223
U2 - 10.1371/journal.pone.0253223
DO - 10.1371/journal.pone.0253223
M3 - SCORING: Journal article
VL - 16
SP - e0253223
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 6
M1 - e0253223
ER -
