Signal dependent ER export of lemur tyrosine kinase 2. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Butler, E.; Bradbury, Neil
• Is Part Of: BMC cell biology. Volume 16:Issue 1(2015)
• Page Start: 1
• Page End: 10
• Publication Date: 2015-12
• Subjects: LMTK2 -- Di-acidic -- ER export -- Transferrin -- Recycling; Cytology -- Periodicals; 571.605
• DOI: 10.1186/s12860-015-0072-6
• Languages: English
• ISSNs: 1471-2121

Abstract

Abstract Background The membrane anchored kinase, LMTK2, is a serine/threonine kinase predominantly localized to endosomal compartments. LMTK2 has been shown to be involved in the trafficking of the CFTR ion channel, the androgen receptor, as well as modulating neurodegeneration. As a membrane anchored protein, LMTK2 must be exported from the ER, yet the mechanisms whereby LMTK2 is sequestered within the ER for efficient export are unknown. Methods Sequence analysis of the carboxyl tail of LMTK2 revealed a putative di-acidic ER export motif. Site-directed mutagenesis was utilized to ablate this potential motif. Subcellular fractionation, immunofluorescence microscopy, and transferrin recycling assays were used to determine the consequence of mutating LMTK2's export motif. Results Mutation of the di-acidic export motif led to ER retention of LMTK2, and an increase in protein half-life and a concomitant loss of LMTK2 from its appropriate terminal destination. Loss of LMTK2 from endosomal compartments by preventing its release from the ER is linked to a reduction in transferrin recycling. Conclusions We have identified a di-acidic ER export motif within the carboxyl tail of the membrane anchored kinase LMTK2. This sequence is used by LMTK2 for its efficient export from the ER.