Post-translational membrane insertion of tail-anchored transmembrane EF-hand Ca2+ sensor calneurons requires the TRC40/Asna1 protein chaperone

Hradsky, Johannes, Raghuram, Vijeta, Reddy, Parameshwar Pasham, Navarro, Gemma, Hupe, Mike, Casado, Vicent, McCormick, Peter J, Sharma, Yogendra, Kreutz, Michael R and Mikhaylova, Marina (2011) Post-translational membrane insertion of tail-anchored transmembrane EF-hand Ca2+ sensor calneurons requires the TRC40/Asna1 protein chaperone. The Journal of Biological Chemistry, 286 (42). pp. 36762-76. ISSN 1083-351X

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Abstract

Calneuron-1 and -2 are neuronal EF-hand-type calcium sensor proteins that are prominently targeted to trans-Golgi network membranes and impose a calcium threshold at the Golgi for phosphatidylinositol 4-OH kinase IIIβ activation and the regulated local synthesis of phospholipids that are crucial for TGN-to-plasma membrane trafficking. In this study, we show that calneurons are nonclassical type II tail-anchored proteins that are post-translationally inserted into the endoplasmic reticulum membrane via an association of a 23-amino acid-long transmembrane domain (TMD) with the TRC40/Asna1 chaperone complex. Following trafficking to the Golgi, calneurons are probably retained in the TGN because of the length of the TMD and phosphatidylinositol 4-phosphate lipid binding. Both calneurons rapidly self-associate in vitro and in vivo via their TMD and EF-hand containing the N terminus. Although dimerization and potentially multimerization precludes TRC40/Asna1 binding and thereby membrane insertion, we found no evidence for a cytosolic pool of calneurons and could demonstrate that self-association of calneurons is restricted to membrane-inserted protein. The dimerization properties and the fact that they, unlike every other EF-hand calmodulin-like Ca(2+) sensor, are always associated with membranes of the secretory pathway, including vesicles and plasma membrane, suggests a high degree of spatial segregation for physiological target interactions.

Item Type: Article
Uncontrolled Keywords: animals,arsenite transporting atpases,cos cells,calcium,calmodulin,cercopithecus aethiops,hek293 cells,hela cells,humans,intracellular membranes,molecular chaperones,protein multimerization,protein structure, tertiary,protein transport,trans-golgi network
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Pure Connector
Date Deposited: 13 Jan 2014 13:20
Last Modified: 21 Apr 2020 22:45
URI: https://ueaeprints.uea.ac.uk/id/eprint/47153
DOI: 10.1074/jbc.M111.280339

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