The role of palmitoylation and transmembrane domain in sorting of transmembrane adaptor proteins

Abstract

Plasma membrane proteins synthesised at the endoplasmic reticulum are delivered to cell surface via sorting pathways. Hydrophobic mismatch theory based on the length of transmembrane domain (TMD) dominates discussion about determinants required for protein sorting to the plasma membrane. Transmembrane adaptor proteins (TRAP) are involved in signalling events taking place at the plasma membrane. Members of this protein family have TMD of varying length. We were interested whether palmitoylation or other motifs contribute to the effective sorting of TRAP proteins. We found that palmitoylation is essential for some but not all TRAP proteins independent of their TMD length. We also provide evidence that palmitoylation and proximal sequences can modulate sorting of artificial proteins with TMD of suboptimal length. Our observations point to a unique character of each TMD defined by its primary amino acid sequence and its impact on membrane protein localisation. We conclude that, in addition to the TMD length, secondary sorting determinants such as palmitoylation or flanking sequences have evolved for the localisation of membrane proteins.