De novo lipid synthesis and polarized prenylation drive cell invasion through basement membrane.
J Cell Biol
; 223(10)2024 10 07.
Article
em En
| MEDLINE
| ID: mdl-39007804
ABSTRACT
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Membrana Basal
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Caenorhabditis elegans
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Proteínas de Caenorhabditis elegans
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Retículo Endoplasmático
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Lipogênese
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article