scholarly journals Identification and dynamics of the DHHC16-DHHC6 palmitoylation cascade

2017 ◽  
Author(s):  
Laurence Abrami ◽  
Tiziano Dallavilla ◽  
Patrick A. Sandoz ◽  
Mustafa Demir ◽  
Béatrice Kunz ◽  
...  

ABSTRACTS-Palmitoylation is the only reversible post-translational lipid modification. Knowledge about the DHHC family of palmitoyltransferases is very limited. Here we show that mammalian DHHC6, which modifies key proteins of the endoplasmic reticulum, is controlled by an upstream palmitoyltransferase, DHHC16, revealing the first palmitoylation cascade. Combination of site specific mutagenesis of the three DHHC6 palmitoylation sites, experimental determination of kinetic parameters and data-driven mathematical modelling allowed us to obtain detailed information on the 8 differentially palmitoylated DHHC6 species. We found that species rapidly interconvert through the action of DHHC16 and the Acyl Protein Thioesterase APT2, that each species varies in terms of turnover rate and activity, altogether allowing the cell to robustly tune its DHHC6 activity.

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Laurence Abrami ◽  
Tiziano Dallavilla ◽  
Patrick A Sandoz ◽  
Mustafa Demir ◽  
Béatrice Kunz ◽  
...  

S-Palmitoylation is the only reversible post-translational lipid modification. Knowledge about the DHHC palmitoyltransferase family is still limited. Here we show that human ZDHHC6, which modifies key proteins of the endoplasmic reticulum, is controlled by an upstream palmitoyltransferase, ZDHHC16, revealing the first palmitoylation cascade. The combination of site specific mutagenesis of the three ZDHHC6 palmitoylation sites, experimental determination of kinetic parameters and data-driven mathematical modelling allowed us to obtain detailed information on the eight differentially palmitoylated ZDHHC6 species. We found that species rapidly interconvert through the action of ZDHHC16 and the Acyl Protein Thioesterase APT2, that each species varies in terms of turnover rate and activity, altogether allowing the cell to robustly tune its ZDHHC6 activity.


2005 ◽  
Vol 87 (11) ◽  
pp. 114102 ◽  
Author(s):  
Hoo-Jeong Lee ◽  
Hai Ni ◽  
David T. Wu ◽  
Ainissa G. Ramirez

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Anthony H. Futerman

Ceramides are a family of sphingophospholipids synthesized in the endoplasmic reticulum, which mediate cell stress responses, including apoptosis, autophagy and senescence, Serine palmitoyltransferase generates 3-ketosphinganine, which is reduced to dihydrosphingosine. N-Acylation allows the formation of dihydroceramides, which are subsequently reduced to form ceramides. Once synthesized, ceramides are trafficked from the ER to the Golgi bound to the ceramide transfer protein, CERT (COL4A3BP, Q9Y5P4). Ceramide can be metabolized via multiple routes, ensuring tight regulation of its cellular levels. Addition of phosphocholine generates sphingomyelin while carbohydrate is added to form glucosyl- or galactosylceramides. Ceramidase re-forms sphingosine or sphinganine from ceramide or dihydroceramide. Phosphorylation of ceramide generates ceramide phosphate. The determination of accurate kinetic parameters for many of the enzymes in the sphingolipid metabolic pathway is complicated by the lipophilic nature of the substrates.


2020 ◽  
Vol 2020 (5) ◽  
Author(s):  
Anthony H. Futerman

Ceramides are a family of sphingophospholipids synthesized in the endoplasmic reticulum, which mediate cell stress responses, including apoptosis, autophagy and senescence, Serine palmitoyltransferase generates 3-ketosphinganine, which is reduced to dihydrosphingosine (dihydrosphingosine). N-Acylation allows the formation of dihydroceramides, which are subsequently reduced to form ceramides. Once synthesized, ceramides are trafficked from the ER to the Golgi bound to the ceramide transfer protein, CERT (COL4A3BP, Q9Y5P4). Ceramide can be metabolized via multiple routes, ensuring tight regulation of its cellular levels. Addition of phosphocholine generates sphingomyelin while carbohydrate is added to form glucosyl- or galactosylceramides. Ceramidase re-forms sphingosine or sphinganine from ceramide or dihydroceramide. Phosphorylation of ceramide generates ceramide phosphate. The determination of accurate kinetic parameters for many of the enzymes in the sphingolipid metabolic pathway is complicated by the lipophilic nature of the substrates.


2003 ◽  
Vol 88 (7) ◽  
pp. 1060-1072 ◽  
Author(s):  
Thráinn Fridriksson ◽  
J. William Carey ◽  
David L. Bish ◽  
Philip S. Neuhoff ◽  
Dennis K. Bird

Author(s):  
Jessica A. Onwuzuruike ◽  
Maruf A. Aminu

The nature of renewable energy resources makes it necessary to perform site-specific resource assessment in order to achieve fairly accurate estimate of energy harvest so as to meet requirements of energy consumption and storage. Available design tools are based largely on remote modeling and estimation of site’s resource potentials. These design tools provide analytical value of the panel generation factor which may not represent the true value. The panel generation factor is used for design of solar photovoltaic systems. This paper reports on the panel generation factor obtained from experimental determination of its value for Apo Area of the Federal Capital Territory in Nigeria. The value of the panel generation factor obtained experimentally for Apo Area is 3.625. The panel generation factor reported in literature for tropical climate of Apo is 3.596. The value obtained for the experimentally determined panel generation factor represents a deviation of 0.88% in comparison with the value reported in literature, validating the value obtained experimentally. The site-specific requirement of renewable energy deployment is indicative of the usefulness of this experimentally determined panel generation factor.


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