Plasma membrane proteins synthesised at the endoplasmic reticulum are delivered to the cell surface via sorting pathways. Hydrophobic mismatch theory based on the length of the transmembrane domain (TMD) dominates discussion about determinants required for protein sorting to the plasma membrane. Transmembrane adaptor proteins (TRAP) are involved in signalling events which take place at the plasma membrane. Members of this protein family have TMDs of varying length. We were interested in 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 TMDs 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.

Department of Biophysical Chemistry J Heyrovsky Institute of Physical Chemistry Czech Academy of Sciences Dolejskova 3 18223 Prague Czech Republic

Department of Biophysical Chemistry J Heyrovsky Institute of Physical Chemistry Czech Academy of Sciences Dolejskova 3 18223 Prague Czech Republic Laboratory of Leukocyte Signaling Institute of Molecule Genetics Czech Academy of Sciences Videnska 1083 Prague Czech Republic

Laboratory of Leukocyte Signaling Institute of Molecule Genetics Czech Academy of Sciences Videnska 1083 Prague Czech Republic

Microscopy Unit Institute of Experimental Medicine Czech Academy of Sciences Videnska 1083 14220 Prague Czech Republic

References provided by Crossref.org