Abstract
| Language | English |
|---|---|
| Pages | 39573-39584 |
| Number of pages | 12 |
| Journal | Journal of Biological Chemistry |
| Volume | 286 |
| Early online date | 18 Sep 2011 |
| DOIs | |
| Publication status | Published - 11 Nov 2011 |
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Keywords
- intracellular trafficking
- membrane trafficking
- protein acylation
- protein palmitoylation
- protein sorting
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Endoplasmic reticulum localization of DHHC palmitoyltransferases mediated by lysine-based sorting signals. / Gorleku, Oforiwa A; Barns, Anna-Marie; Prescott, Gerald R; Greaves, Jennifer; Chamberlain, Luke H.
In: Journal of Biological Chemistry , Vol. 286, 11.11.2011, p. 39573-39584.Research output: Contribution to journal › Article
TY - JOUR
T1 - Endoplasmic reticulum localization of DHHC palmitoyltransferases mediated by lysine-based sorting signals
AU - Gorleku, Oforiwa A
AU - Barns, Anna-Marie
AU - Prescott, Gerald R
AU - Greaves, Jennifer
AU - Chamberlain, Luke H
PY - 2011/11/11
Y1 - 2011/11/11
N2 - Intracellular palmitoylation dynamics are regulated by a family of 24 DHHC palmitoyl transferases, which are localized in a compartment-specific manner. The majority of DHHC proteins localize to endoplasmic reticulum (ER) and Golgi membranes, and a small number target to post-Golgi membranes. To-date, there are no reports of the fine mapping of sorting signals in mammalian DHHC proteins, and thus it is unclear how spatial distribution of the DHHC family is achieved. Here, we have identified and characterized lysine-based sorting signals that determine the restricted localization of DHHC4 and DHHC6 to ER membranes. The ER targeting signal in DHHC6 conforms to a KKxx motif, whereas the signal in DHHC4 is a distinct Kxx motif. The identified dilysine signals are sufficient to specify ER localization as adding the C-terminal pentapeptide sequences from DHHC4 or DHHC6, which contain these Kxx and KKxx motifs, to the C-terminus of DHHC3 redistributes this palmitoyl transferase from Golgi to ER membranes. Recent work proposed that palmitoylation of newly-synthesized peripheral membrane proteins occurs predominantly at the Golgi. Indeed, previous analyses of the peripheral membrane proteins, SNAP25 and cysteine-string protein is fully consistent with their initial palmitoylation being mediated by Golgi-localized DHHC proteins. Interestingly, ER-localized DHHC3 is able to palmitoylate SNAP25 and cysteine-string protein to a similar level as wild-type Golgi-localized DHHC3 in co-expression studies. These results suggest that targeting of intrinsically active DHHC proteins to defined membrane compartments is an important factor contributing to spatially-restricted patterns of substrate palmitoylation. compartments.
AB - Intracellular palmitoylation dynamics are regulated by a family of 24 DHHC palmitoyl transferases, which are localized in a compartment-specific manner. The majority of DHHC proteins localize to endoplasmic reticulum (ER) and Golgi membranes, and a small number target to post-Golgi membranes. To-date, there are no reports of the fine mapping of sorting signals in mammalian DHHC proteins, and thus it is unclear how spatial distribution of the DHHC family is achieved. Here, we have identified and characterized lysine-based sorting signals that determine the restricted localization of DHHC4 and DHHC6 to ER membranes. The ER targeting signal in DHHC6 conforms to a KKxx motif, whereas the signal in DHHC4 is a distinct Kxx motif. The identified dilysine signals are sufficient to specify ER localization as adding the C-terminal pentapeptide sequences from DHHC4 or DHHC6, which contain these Kxx and KKxx motifs, to the C-terminus of DHHC3 redistributes this palmitoyl transferase from Golgi to ER membranes. Recent work proposed that palmitoylation of newly-synthesized peripheral membrane proteins occurs predominantly at the Golgi. Indeed, previous analyses of the peripheral membrane proteins, SNAP25 and cysteine-string protein is fully consistent with their initial palmitoylation being mediated by Golgi-localized DHHC proteins. Interestingly, ER-localized DHHC3 is able to palmitoylate SNAP25 and cysteine-string protein to a similar level as wild-type Golgi-localized DHHC3 in co-expression studies. These results suggest that targeting of intrinsically active DHHC proteins to defined membrane compartments is an important factor contributing to spatially-restricted patterns of substrate palmitoylation. compartments.
KW - intracellular trafficking
KW - membrane trafficking
KW - protein acylation
KW - protein palmitoylation
KW - protein sorting
UR - http://www.scopus.com/inward/record.url?scp=80655128141&partnerID=8YFLogxK
U2 - 10.1074/jbc.M111.272369
DO - 10.1074/jbc.M111.272369
M3 - Article
VL - 286
SP - 39573
EP - 39584
JO - Journal of Biological Chemistry
T2 - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
ER -