A lipid flippase shapes the ciliary membrane and is essential for ciliogenesis.
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| Autores principales: | , , , , , |
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| Formato: | Artículo científico |
| Lenguaje: | en |
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Current biology : CB
2025
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| _version_ | 1868266130298109953 |
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| author | Wang, Zhengmao He, Ruida Liu, Qingqing Snell, William J Cao, Muqing Pan, Junmin |
| author_facet | Wang, Zhengmao He, Ruida Liu, Qingqing Snell, William J Cao, Muqing Pan, Junmin Wang, Zhengmao He, Ruida Liu, Qingqing Snell, William J Cao, Muqing Pan, Junmin |
| collection | PubMed - marine biology |
| contents | A lipid flippase shapes the ciliary membrane and is essential for ciliogenesis. Wang, Zhengmao He, Ruida Liu, Qingqing Snell, William J Cao, Muqing Pan, Junmin Cilia Animals Humans Chlamydomonas reinhardtii Phospholipid Transfer Proteins Cell Membrane Ciliary motility and signaling are essential for human development and homeostasis. Although assembly of the microtubule-based core of the cilium, the axoneme, is well studied, we know little about formation of the cylindrically shaped ciliary membrane. During ciliogenesis, and in seamless coordination with the assembly of the axoneme, this membrane is built from the lipid bilayers of pre-ciliary membrane vesicles delivered near the base of the organelle. Upon vesicle exocytosis, their membrane curvature must be reversed as they become incorporated into the oppositely curved ciliary membrane. Here, we report that aminophospholipid flippases regulate the lipid composition of the outer leaflet of the ciliary membrane and are critical determinants of ciliary membrane shape and ciliogenesis. In mammalian cells, depletion of flippases results in fewer and shorter cilia. Upon initiation of ciliogenesis in Chlamydomonas, aminophospholipid flippase 2 (ALA2) is rapidly recruited laterally from the plasma membrane to the nascent ciliary membrane, where it appears as a C-terminally truncated form. Phosphatidylethanolamine (PE) is aberrantly enriched in the outer leaflet of the ciliary membrane of ala2 and ala1;ala2 mutants. Absence of ALA2 alone leads to diminished ciliary length, ciliary swelling, and frequent organelle detachment. In the double mutants, all newly formed cilia detach soon after ciliogenesis begins. This work reveals that the flippase-regulated lipid composition of the outer leaflet of the ciliary membrane determines the membrane curvature of this essential organelle, with implications for membrane remodeling in health and disease. |
| format | Artículo científico |
| id | pubmed_41197635 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Current biology : CB |
| record_format | pubmed |
| spellingShingle | A lipid flippase shapes the ciliary membrane and is essential for ciliogenesis. Wang, Zhengmao He, Ruida Liu, Qingqing Snell, William J Cao, Muqing Pan, Junmin Cilia Animals Humans Chlamydomonas reinhardtii Phospholipid Transfer Proteins Cell Membrane A lipid flippase shapes the ciliary membrane and is essential for ciliogenesis. Wang, Zhengmao He, Ruida Liu, Qingqing Snell, William J Cao, Muqing Pan, Junmin Cilia Animals Humans Chlamydomonas reinhardtii Phospholipid Transfer Proteins Cell Membrane Ciliary motility and signaling are essential for human development and homeostasis. Although assembly of the microtubule-based core of the cilium, the axoneme, is well studied, we know little about formation of the cylindrically shaped ciliary membrane. During ciliogenesis, and in seamless coordination with the assembly of the axoneme, this membrane is built from the lipid bilayers of pre-ciliary membrane vesicles delivered near the base of the organelle. Upon vesicle exocytosis, their membrane curvature must be reversed as they become incorporated into the oppositely curved ciliary membrane. Here, we report that aminophospholipid flippases regulate the lipid composition of the outer leaflet of the ciliary membrane and are critical determinants of ciliary membrane shape and ciliogenesis. In mammalian cells, depletion of flippases results in fewer and shorter cilia. Upon initiation of ciliogenesis in Chlamydomonas, aminophospholipid flippase 2 (ALA2) is rapidly recruited laterally from the plasma membrane to the nascent ciliary membrane, where it appears as a C-terminally truncated form. Phosphatidylethanolamine (PE) is aberrantly enriched in the outer leaflet of the ciliary membrane of ala2 and ala1;ala2 mutants. Absence of ALA2 alone leads to diminished ciliary length, ciliary swelling, and frequent organelle detachment. In the double mutants, all newly formed cilia detach soon after ciliogenesis begins. This work reveals that the flippase-regulated lipid composition of the outer leaflet of the ciliary membrane determines the membrane curvature of this essential organelle, with implications for membrane remodeling in health and disease. |
| title | A lipid flippase shapes the ciliary membrane and is essential for ciliogenesis. |
| topic | Cilia Animals Humans Chlamydomonas reinhardtii Phospholipid Transfer Proteins Cell Membrane |
| url | https://pubmed.ncbi.nlm.nih.gov/41197635/ |