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Structure. 2015 Feb 3;23(2):364-73. doi: 10.1016/j.str.2014.11.016. Epub 2015 Jan 8.

The LisH motif of muskelin is crucial for oligomerization and governs intracellular localization.

Author information

1
Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, D-97080 Würzburg, Germany.
2
Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, D-20251 Hamburg, Germany.
3
Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, D-97080 Würzburg, Germany. Electronic address: hermann.schindelin@virchow.uni-wuerzburg.de.

Abstract

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.

PMID:
25579817
DOI:
10.1016/j.str.2014.11.016
[Indexed for MEDLINE]
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