Characterizing Palmitoylation of the Sodium Hydrogen Exchanger Isoform 1 (NHE1) (original) (raw)

Palmitoylation of ATP-Binding Cassette Transporter A1 Is

2015

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The Dynamic Role of Palmitoylation In Signal Transduction

Trends in biochemical sciences, 1995

Guanine nucleotide binding p:otein (G protein)4inked receptors, the a-subunits of heterotdmedc G proteins and members of the Src family of nonreceptor tyrosine kinases are among many polypeptides that are posttransmationally modified by the addition of palmitate, a mong-chain fatty acid. Attachment of pNmitate to these protein3 is dynamic and may be regulated by their activation. The presence of palmitate appears to pJay a key role in the membrane localization of either the entire polypeptide or parts of it, and may regugate the interactions of these polypeptides with other proteins. ~E~PJ~I'~ OF ,~l~oW'l~. +4P+h LIFE LIFE. ~'~ ~IJTrLE INT~£CT" "/~ O)tR C[41.TkR'P.. ~XEP.cI~.5,/~FTe~ ~ pe,~, THe. PH/~Pf g~'me~s 7He [ Se~lj t~S IT £F.comes ~ST ¢(k~4S, pX..~ ~LCeNjT~ ~ ~Tm~ 7 HIIq SELF. YeM~ t~lk'Nce ~hY No'r

Structure and function of the NHE1 isoform of the Na+/H+exchanger

Biochemistry and Cell Biology, 2002

The Na+/H+exchanger is a ubiquitous, integral membrane protein involved in pH regulation. It removes intracellular acid, exchanging a proton for an extracellular sodium ion. There are seven known isoforms of this protein that are the products of distinct genes. The first isoform discovered (NHE1) is ubiquitously distributed throughout the plasma membrane of virtually all tissues. It plays many different physiological roles in mammals, including important functions in regulation of intracellular pH, in heart disease, and in cytoskeletal organization. The first 500 amino acids of the protein are believed to consist of 12 transmembrane helices, a membrane-associated segment, and two reentrant loops. A C-terminal regulatory domain of approximately 315 amino acids regulates the protein and mediates cyto skel etal interactions. Studies are underway to determine the amino acid residues important in NHE1 function. At present, it is clear that transmembrane segment IV is important in NHE1 fu...

On the mechanism of protein palmitoylation

EMBO reports, 2004

Protein palmitoylation or, more specifically, S-acylation is a reversible post-translational lipid modification. Despite the identification of several proteins that are altered in this way, our understanding of the enzymology of this process has been hampered by the lack of well-characterized acyltransferases. We now know of three proteins in Saccharomyces cerevisiae that promote palmitoylation: effector of Ras function (Erf2), ankyrin-repeat-containing protein (Akr1) and the SNARE protein Ykt6. Erf2 and Akr1 are integral membrane proteins that contain a cysteine-rich domain and an Asp-His-His-Cys motif, both of which catalyse acylation at the carboxyl terminus of their target proteins. Recently, we discovered that Ykt6 mediates the amino-terminal acylation of the fusion protein Vac8. Even though these three proteins differ in sequence, topology, size and substrate specificity, they might function in a similar manner. In this review, we discuss these observations in the context of a potential general mechanism of acylation.

Labeling and quantifying sites of protein palmitoylation

BioTechniques, 2004

As a reversible posttranslational modification, protein palmitoylation has the potential to regulate the trafficking and function of a variety of proteins. However, the extent, function, and dynamic nature of palmitoylation are poorly resolved because of limitations in assay methods. Here, we introduce methods where hydroxylamine-mediated cleavage of the palmitoyl-thioester bond generates a free sulfhydryl, which can then be specifically labeled with sulfhydryl-reactive reagents. This methodology is more sensitive and allows for quantitative estimates of palmitoylation. Unlike other techniques used to assay posttranslational modifications, the techniques we have developed can label all sites of modification with a variety of probes, radiolabeled or nonradioactive, and can be used to assay the palmitoylation of proteins expressed in vivo in brain or other tissues.

Palmitoylation and depalmitoylation dynamics at a glance

Journal of Cell Science, 2010

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 palmitoylationthe 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 G i 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