Plasma membrane (PM) lipid composition and domain organization are modulated by polarized exocytosis. Conversely, targeting of secretory vesicles at specific domains in the PM is carried out by exocyst complexes, which contain EXO70 subunits that play a significant role in the final recognition of the target membrane. As we have shown previously, a mature Arabidopsis trichome contains a basal domain with a thin cell wall and an apical domain with a thick secondary cell wall, which is developed in an EXO70H4-dependent manner. These domains are separated by a cell wall structure named the Ortmannian ring. Using phospholipid markers, we demonstrate that there are two distinct PM domains corresponding to these cell wall domains. The apical domain is enriched in phosphatidic acid (PA) and phosphatidylserine, with an undetectable amount of phosphatidylinositol 4,5-bisphosphate (PIP2), whereas the basal domain is PIP2-rich. While the apical domain recruits EXO70H4, the basal domain recruits EXO70A1, which corresponds to the lipid-binding capacities of these two paralogs. Loss of EXO70H4 results in a loss of the Ortmannian ring border and decreased apical PA accumulation, which causes the PA and PIP2 domains to merge together. Using transmission electron microscopy, we describe these accumulations as a unique anatomical feature of the apical cell wall-radially distributed rod-shaped membranous pockets, where both EXO70H4 and lipid markers are immobilized.

• MeSH
• Arabidopsis chemie   genetika   MeSH
• buněčná membrána chemie   genetika   MeSH
• exocytóza genetika   MeSH
• fosfatidylinositol-4,5-difosfát chemie   metabolismus   MeSH
• fosfatidylseriny chemie   genetika   MeSH
• membránové lipidy genetika   metabolismus   MeSH
• proteiny huseníčku chemie   genetika   MeSH
• trichomy chemie   genetika   MeSH
• vezikulární transportní proteiny chemie   genetika   MeSH
• Publikační typ
• časopisecké články MeSH

Lenz-Majewski syndrome (LMS) is a syndrome of intellectual disability and multiple congenital anomalies that features generalized craniotubular hyperostosis. By using whole-exome sequencing and selecting variants consistent with the predicted dominant de novo etiology of LMS, we identified causative heterozygous missense mutations in PTDSS1, which encodes phosphatidylserine synthase 1 (PSS1). PSS1 is one of two enzymes involved in the production of phosphatidylserine. Phosphatidylserine synthesis was increased in intact fibroblasts from affected individuals, and end-product inhibition of PSS1 by phosphatidylserine was markedly reduced. Therefore, these mutations cause a gain-of-function effect associated with regulatory dysfunction of PSS1. We have identified LMS as the first human disease, to our knowledge, caused by disrupted phosphatidylserine metabolism. Our results point to an unexplored link between phosphatidylserine synthesis and bone metabolism.

• MeSH
• dánio pruhované embryologie   genetika   MeSH
• dítě MeSH
• embryo nesavčí MeSH
• fibroblasty metabolismus   MeSH
• fosfatidylseriny biosyntéza   genetika   MeSH
• hyperostóza MeSH
• kultivované buňky MeSH
• lidé MeSH
• mladiství MeSH
• mnohočetné abnormality genetika   MeSH
• molekulární sekvence - údaje MeSH
• mutace * MeSH
• nanismus MeSH
• syndrom MeSH
• transferasy dusíkatých skupin genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH