The LisH Motif of Muskelin Is Crucial for Oligomerization and Governs Intracellular Localization
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The LisH Motif of Muskelin Is Crucial for Oligomerization and Governs Intracellular Localization. / Delto, Carolyn F; Heisler, Frank F; Kuper, Jochen; Sander, Bodo; Kneussel, Matthias; Schindelin, Hermann.
In: STRUCTURE, Vol. 23, No. 2, 03.02.2015, p. 364-73.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The LisH Motif of Muskelin Is Crucial for Oligomerization and Governs Intracellular Localization
AU - Delto, Carolyn F
AU - Heisler, Frank F
AU - Kuper, Jochen
AU - Sander, Bodo
AU - Kneussel, Matthias
AU - Schindelin, Hermann
N1 - Copyright © 2015 Elsevier Ltd. All rights reserved.
PY - 2015/2/3
Y1 - 2015/2/3
N2 - Neurons regulate the number of surface receptors by balancing the transport to and from the plasma membrane to adjust their signaling properties. The protein muskelin was recently identified as a key factor guiding the transport of α1 subunit-containing GABAA receptors. Here we present the crystal structure of muskelin, comprising its N-terminal discoidin domain and Lis1-homology (LisH) motif. The molecule crystallized as a dimer with the LisH motif exclusively mediating oligomerization. Our subsequent biochemical analyses confirmed that the LisH motif acts as a dimerization element in muskelin. Together with an intermolecular head-to-tail interaction, the LisH-dependent dimerization is required to assemble a muskelin tetramer. Intriguingly, our cellular studies revealed that the loss of this dimerization results in a complete redistribution of muskelin from the cytoplasm to the nucleus and impairs muskelin's function in GABAA receptor transport. These studies demonstrate that the LisH-dependent dimerization is a crucial factor for muskelin function.
AB - Neurons regulate the number of surface receptors by balancing the transport to and from the plasma membrane to adjust their signaling properties. The protein muskelin was recently identified as a key factor guiding the transport of α1 subunit-containing GABAA receptors. Here we present the crystal structure of muskelin, comprising its N-terminal discoidin domain and Lis1-homology (LisH) motif. The molecule crystallized as a dimer with the LisH motif exclusively mediating oligomerization. Our subsequent biochemical analyses confirmed that the LisH motif acts as a dimerization element in muskelin. Together with an intermolecular head-to-tail interaction, the LisH-dependent dimerization is required to assemble a muskelin tetramer. Intriguingly, our cellular studies revealed that the loss of this dimerization results in a complete redistribution of muskelin from the cytoplasm to the nucleus and impairs muskelin's function in GABAA receptor transport. These studies demonstrate that the LisH-dependent dimerization is a crucial factor for muskelin function.
U2 - 10.1016/j.str.2014.11.016
DO - 10.1016/j.str.2014.11.016
M3 - SCORING: Journal article
C2 - 25579817
VL - 23
SP - 364
EP - 373
JO - STRUCTURE
JF - STRUCTURE
SN - 0969-2126
IS - 2
ER -