The LisH Motif of Muskelin Is Crucial for Oligomerization and Governs Intracellular Localization

作者：Delto Carolyn F; Heisler Frank F; Kuper Jochen; Sander Bodo; Kneussel Matthias; Schindelin Hermann^*

来源：Structure, 2015, 23(2): 364-373.

DOI：10.1016/j.str.2014.11.016

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 alpha 1 subunit-containing GABA(A) 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.

• 出版日期2015-2-3