Palmitoylation and depalmitoylation dynamics at a glance.

Protein palmitoylation, the thioester linkage of fatty acyl moieties (typically, saturated 16C palmitate) to cysteine, is a lipid modification that serves both to tether proteins to membranes and to direct their localization to membrane microdomains. Unlike the two other types of lipid modification that also tether proteins to cytosolic membrane surfaces, namely prenylation and myristoylation, which remain attached to the protein throughout its lifetime, a distinguishing feature of palmitoylation is its reversibility. This ‘At a Glance’ poster article focuses on this one aspect of palmitoylation – the dynamic regulation of membrane association of proteins through the regulated addition and removal of palmitoyl modifications. Other aspects of protein palmitoylation are covered in a number of recent reviews (Fukata et al., 2004; Nadolski and Linder, 2007; Planey and Zacharias, 2009; Zeidman et al., 2009). The Ras proto-oncogene family members H-Ras and N-Ras (hereafter referred to as H/N-Ras) provide the best example of proteins whose localization is dynamically regulated by reversible palmitoylation (see Poster, panel 1). Palmitoylation at the Golgi stabilizes the association of H/N-Ras with membranes, thereby facilitating its vesicular trafficking to the plasma membrane (PM). There, depalmitoylation releases H/N-Ras into the cytoplasm, allowing its return to the Golgi for another round of palmitoylation. Because the Golgi and the PM pools of H/N-Ras activate different downstream signaling cascades (Fehrenbacher et al., 2009), this regulation of localization also regulates signaling. Similar palmitoylation-driven protein cycling between Golgi and PM has been documented for several other signaling regulators, including the heterotrimeric G-protein subunit Gi and the non-receptor tyrosine kinase Fyn (Rocks et al., 2010; Rocks et al., 2005) (see Poster, panel 4). Nonetheless, it remains unclear how widely the Ras paradigm applies. Below, we focus on the Ras cycle as an example of how palmitoylation and depalmitoylation act to dynamically regulate protein localization. We