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CFAP418 participates in membrane-associated cellular processes through binding lipids during ciliogenesis

ABSTRACT: Ciliopathies and retinal degenerative diseases are heterogeneous groups of genetic diseases. CFAP418 is a causative gene of both diseases, and its sequence is evolutionarily conserved. Here, we employ affinity purification coupled with mass spectrometry and quantitative lipidomic, proteomic, and phosphoproteomic approaches to address the function of CFAP418 in retinas. We show CFAP418 unexpectedly binds to lipid metabolism precursor phosphatidic acid (PA) and mitochondrion-specific lipid cardiolipin but does not form a tight and static complex with proteins. Loss of Cfap418 leads to a widespread disruption of membrane lipid homeostasis and changes in protein-membrane association, which subsequently causes mitochondrial morphological and functional defects and membrane remodeling abnormalities in multiple vesicular trafficking pathways. The signaling of PA-binding protein kinase Ca is increased. Our results indicate that membrane lipid imbalance is a new pathological mechanism underlying inherited ciliopathies and retinal degenerations, which is associated with other known causative RAB28 and BBS genes.

ORGANISM(S): Mouse Mus Musculus

TISSUE(S): Eye Tissue

DISEASE(S): Eye Disease

SUBMITTER: John Maschek

PROVIDER: ST002162 | MetabolomicsWorkbench | Tue May 10 00:00:00 BST 2022

REPOSITORIES: MetabolomicsWorkbench

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CFAP418 participates in membrane-associated cellular processes through binding lipids during ciliogenesis

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