De novo lipid synthesis and polarized prenylation drive cell invasion through basement membrane.
| Autor: | Park K; Department of Biology, Duke University, Durham, NC, USA., Garde A; Department of Molecular Biology, Princeton University, Princeton, NJ, USA.; Howard Hughes Medical Institute, Princeton University, Princeton, NJ, USA., Thendral SB; Department of Biology, Duke University, Durham, NC, USA., Soh AWJ; Department of Biology, Duke University, Durham, NC, USA., Chi Q; Department of Biology, Duke University, Durham, NC, USA., Sherwood DR; Department of Biology, Duke University, Durham, NC, USA. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of cell biology [J Cell Biol] 2024 Oct 07; Vol. 223 (10). Date of Electronic Publication: 2024 Jul 15. |
| DOI: | 10.1083/jcb.202402035 |
| Abstrakt: | To breach the basement membrane, cells in development and cancer use large, transient, specialized lipid-rich membrane protrusions. Using live imaging, endogenous protein tagging, and cell-specific RNAi during Caenorhabditis elegans anchor cell (AC) invasion, we demonstrate that the lipogenic SREBP transcription factor SBP-1 drives the expression of the fatty acid synthesis enzymes POD-2 and FASN-1 prior to invasion. We show that phospholipid-producing LPIN-1 and sphingomyelin synthase SMS-1, which use fatty acids as substrates, produce lysosome stores that build the AC's invasive protrusion, and that SMS-1 also promotes protrusion localization of the lipid raft partitioning ZMP-1 matrix metalloproteinase. Finally, we discover that HMG-CoA reductase HMGR-1, which generates isoprenoids for prenylation, localizes to the ER and enriches in peroxisomes at the AC invasive front, and that the final transmembrane prenylation enzyme, ICMT-1, localizes to endoplasmic reticulum exit sites that dynamically polarize to deliver prenylated GTPases for protrusion formation. Together, these results reveal a collaboration between lipogenesis and a polarized lipid prenylation system that drives invasive protrusion formation. (© 2024 Park et al.) |
| Databáze: | MEDLINE |
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