Post-translational Membrane Insertion of Tail-anchored Transmembrane EF-hand Ca2+ Sensor Calneurons Requires the TRC40/Asna1 Protein Chaperone

Autor: Vijeta Raghuram, Johannes Hradsky, Marina Mikhaylova, Peter J. McCormick, Michael R. Kreutz, Parameshwar Pasham Reddy, Gemma Navarro, Yogendra Sharma, Mike Hupe, Vicent Casadó
Rok vydání: 2011
Předmět:
metabolism [trans-Golgi Network]
Biology
Biochemistry
metabolism [Intracellular Membranes]
symbols.namesake
genetics [Molecular Chaperones]
Calmodulin
Membrane Biology
Chlorocebus aethiops
CALN1 protein
human
Animals
Humans
metabolism [Calcium]
metabolism [Molecular Chaperones]
Molecular Biology
genetics [Arsenite Transporting ATPases]
Secretory pathway
Arsenite Transporting ATPases
Endoplasmic reticulum
metabolism [Arsenite Transporting ATPases]
genetics [Calmodulin]
Intracellular Membranes
Cell Biology
Golgi apparatus
Transmembrane protein
metabolism [Calmodulin]
GET3 protein
human
Protein Structure
Tertiary
Cell biology
Transport protein
Protein Transport
Transmembrane domain
HEK293 Cells
Membrane protein
physiology [Protein Multimerization]
ddc:540
genetics [trans-Golgi Network]
COS Cells
symbols
Chaperone complex
physiology [Protein Transport]
Calcium
Protein Multimerization
HeLa Cells
Molecular Chaperones
trans-Golgi Network
Zdroj: The journal of biological chemistry 286(42), 36762-36776 (2011). doi:10.1074/jbc.M111.280339
ISSN: 0021-9258
DOI: 10.1074/jbc.m111.280339
Popis: 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.
Databáze: OpenAIRE
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