CCN3 secretion is regulated by palmitoylation via ZDHHC22
Normal extracellular secretion of nephroblastoma overexpressed (NOV, also known as CCN3) is important for the adhesion, migration, and differentiation of cells. In previous studies, we have shown that the intracellular accumulation of CCN3 inhibits the growth of prominent neurons. Increased intracel...
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Veröffentlicht in: | Biochemical and biophysical research communications 2018-01, Vol.495 (4), p.2573-2578 |
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Sprache: | eng |
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Zusammenfassung: | Normal extracellular secretion of nephroblastoma overexpressed (NOV, also known as CCN3) is important for the adhesion, migration, and differentiation of cells. In previous studies, we have shown that the intracellular accumulation of CCN3 inhibits the growth of prominent neurons. Increased intracellular CCN3 can be induced through various processes, such as transcription, detoxification, and posttranslational modification. In general, posttranslational modifications are very important for protein secretion. However, it is unclear whether posttranslational modification is necessary for CCN3 secretion. In this study, we have conducted mutational analysis of CCN3 to demonstrate that its thrombospondin type-1 (TSP1) domain is important for CCN3 secretion and intracellular function. Point mutation analysis confirmed that CCN3 secretion was inhibited by cysteine (C)241 mutation, and overexpression of CCN3-C241A inhibited neuronal axonal growth in vivo. Furthermore, we demonstrated that palmitoylation is important for the extracellular secretion of CCN3 and that zinc finger DHHC-type containing 22 (ZDHHC22), a palmityoltransferase, can interact with CCN3. Taken together, our results suggest that palmitoylation by ZDHHC22 at C241 in the CCN3 TSP1 domain may be required for the secretion of CCN3. Aberrant palmitoylation induces intracellular accumulation of CCN3, inhibiting neuronal axon growth.
•The CCN3 thrombospondin type-1 (TSP1) domain is required for its secretion.•The TSP1 domain is also involved in CNN3 intracellular function.•Residue C241 is important for CNN3 secretion, but not its intracellular function.•Palmitoylation at C241 is necessary for CCN3 secretion.•Zinc finger DHHC-type containing 22 interacts with CCN3. |
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ISSN: | 0006-291X 1090-2104 |
DOI: | 10.1016/j.bbrc.2017.12.128 |