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

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