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bioRxiv · 10.1101/2024.10.01.616164

The C. elegans LON-1 protein requires its CAP domain for function in regulating body size and BMP signaling

Serrano, M. V.·Cottier, S.·Wang, L.·Moreira-Antepara, S.·Nzessi, A.·Liu, Z.·Williams, B.·Lee, M.·Schneiter, R.·Liu, J.
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Abstract

The CAP (Cysteine-rich secretory proteins, Antigen-5, Pathogenesis-Related) proteins are widely expressed and have been implicated to play diverse roles ranging from mammalian reproduction to plant immune response. Increasing evidence supports a role of CAP proteins in lipid binding. The C. elegans CAP protein LON-1 is known to regulate body size and Bone Morphogenetic Protein (BMP) signaling. LON-1 is a secreted protein with a conserved CAP domain and a C-terminal unstructured domain with no homology to other proteins. In this study, we report that the C-Terminal Domain (CTD) of LON-1 is dispensable for its function. Instead, key conserved residues located in the CAP domain are critical for LON-1 function in vivo. We further showed that LON-1 is capable of binding sterol, but not fatty acid, in vitro, and that certain key residues implicated in LON-1 function in vivo are also important for LON-1 sterol binding in vitro. These findings suggest a role of LON-1 in regulating body size and BMP signaling via sterol binding. ARTICLE SUMMARYThe C. elegans LON-1 protein is known to regulate body size and Bone Morphogenetic Protein (BMP) signaling. However, its molecular mode of action remains elusive. This study shows that LON-1 can bind sterol, but not fatty acid, in vitro. Furthermore, key conserved residues in the CAP domain of LON-1 are required for LON-1 function in vivo. These findings suggest a role of LON-1 in regulating body size and BMP signaling via sterol binding.

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Serrano, M. V., Cottier, S., Wang, L., Moreira-Antepara, S., Nzessi, A., Liu, Z., Williams, B., Lee, M., Schneiter, R., Liu, J.. 2024-10-03. The C. elegans LON-1 protein requires its CAP domain for function in regulating body size and BMP signaling. https://doi.org/10.1101/2024.10.01.616164

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