Abstract
BackgroundTail anchored (TA) membrane proteins target subcellular structures via a C-terminal transmembrane domain and serve prominent roles in membrane fusion and vesicle transport. Sarcolemmal Membrane Associated Protein (SLMAP) possesses two alternatively spliced tail anchors (TA1 or TA2) but their specificity of subcellular targeting remains unknown.ResultsTA1 or TA2 can direct SLMAP to reticular structures including the endoplasmic reticulum (ER), whilst TA2 directs SLMAP additionally to the mitochondria. Despite the general structural similarity of SLMAP to other vesicle trafficking proteins, we found no evidence for its localization with the vesicle transport machinery or a role in vesicle transport. The predicted transmembrane region of TA2 is flanked on either side by a positively charged amino acid and is itself less hydrophobic than the transmembrane helix present in TA1. Substitution of the positively charged amino acids, in the regions flanking the transmembrane helix of TA2, with leucine did not alter its subcellular targeting. The targeting of SLMAP to the mitochondria was dependent on the hydrophobic nature of TA2 since targeting of SLMAP-TA2 was prevented by the substitution of leucine (L) for moderately hydrophobic amino acid residues within the transmembrane region. The SLMAP-TA2-4L mutant had a hydrophobic profile that was comparable to that of SLMAP-TA1 and had identical targeting properties to SLMAP-TA1.ConclusionThus the overall hydrophobicity of the two alternatively spliced TAs in SLMAP determines its subcellular targeting and TA2 predominantly directs SLMAP to the mitochondira where it may serve roles in the function of this organelle.
Highlights
Tail anchored (TA) membrane proteins target subcellular structures via a Cterminal transmembrane domain and serve prominent roles in membrane fusion and vesicle transport
Our analysis indicates that SLMAP1 itself is not involved in vesicle transport but can target the endoplasmic reticulum (ER) as well as the mitochondria, possibly the MOM, where it may play previously unrecognized roles in the subcellular function of these organelles
Sarcolemmal Membrane Associated Protein (SLMAP) is a component of intracellular membranes in nonmuscle cells The SR is derived from smooth endoplasmic reticulum, an extensive membrane-bound organelle, which contributes to general intracellular calcium regulation in eukaryotic cells [33]
Summary
Tail anchored (TA) membrane proteins target subcellular structures via a Cterminal transmembrane domain and serve prominent roles in membrane fusion and vesicle transport. The tail-anchored (TA) membrane proteins include diverse family members such as cytochrome b5, DMPK A, & C, Bcl-2, Tom, and Sec b & g which are critical for cell function [1,2,3,4,5,6,7,8] Several of these proteins, such as Synaptobrevin, are important in vesicle transport and membrane fusion [9]. Some TAs which target proteins to the MOM, are flanked by positively-charged residues adjacent to the membrane-spanning region which are believed to dictate their targeting to either the ER, or both the ER and the MOM [2,24,25,26] This has led to the view that the p ositive charges individually or collectively in and around the TA determines its subcellular targeting [21,26]. Each SLMAP isoform shares the C-terminal region of the protein but the smaller isoforms do not possess the N-terminal structures such as the FHA domain [8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
