Unc-51-like kinase (ULK) family serine-threonine protein kinase homologues have been linked to the function of motile cilia in diverse species. Mutations in Fused/STK36 and ULK4 in mice resulted in hydrocephalus and other phenotypes consistent with ciliary defects. How either protein contributes to the assembly and function of motile cilia is not well understood. Here we studied the phenotypes of and gene knockout (KO) mutants in the flagellated protist . Both KO mutants exhibited a variety of structural defects of the flagellum cytoskeleton. Biochemical approaches indicate spatial proximity of these proteins and indicate a direct interaction between the N-terminus of LmxULK4 and LmxFused. Both proteins display a dispersed localization throughout the cell body and flagellum, with enrichment near the flagellar base and tip. The stable expression of LmxULK4 was dependent on the presence of LmxFused. Fused/STK36 was previously shown to localize to mammalian motile cilia, and we demonstrate here that ULK4 also localizes to the motile cilia in mouse ependymal cells. Taken together these data suggest a model where the pseudokinase ULK4 is a positive regulator of the kinase Fused/ STK36 in a pathway required for stable assembly of motile cilia.
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http://dx.doi.org/10.1091/mbc.E22-06-0222 | DOI Listing |
Methods Mol Biol
January 2025
Centre for Developmental Neurobiology, King's College London, London, UK.
The choroid plexus (ChP) is a vital brain structure that produces cerebrospinal fluid (CSF) and forms a selective barrier between the blood and CSF, essential for brain homeostasis. Composed of secretory epithelial cells, connective stroma, and a fenestrated vascular network, the ChP supports nutrient transport, immune surveillance, and the clearance of toxic by-products. Despite its significance in maintaining cerebral function, the mechanisms underlying its development and maturation remain poorly understood.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Biological Science, Sookmyung Women's University, Seoul, 04310, Republic of Korea.
Primary cilia are sensory organelles that regulate various signaling pathways. When microtubules are compared to a highway, motor proteins carry and transport cargo proteins, which are tuned by post-translational modifications, such as acetylation. However, the role of acetylation in primary cilia regulation remains unclear.
View Article and Find Full Text PDFCell Death Dis
January 2025
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors because of its high metastatic ability. The glutamine (Gln)-deficient microenvironment contributes to PDAC metastasis; however, the underlying molecular mechanisms remain unclear. Here, we demonstrated that melanophilin (MLPH) promotes PDAC metastasis by inducing the regrowth of primary cilia.
View Article and Find Full Text PDFSci Prog
January 2025
Department of Biochemistry and Molecular Biology, School of Preclinical Medicine, Zunyi Medical University, Zunyi, Guizhou, China.
Vangl2, a core component of the PCP signaling pathway, serves as a scaffold protein on the cell membrane, playing a crucial role in organizing protein complexes. Cilia, dynamic structures on the cell surface, carry out a wide range of functions. Research has highlighted a bidirectional regulatory interaction between Vangl2 and cilia, underscoring their interconnected roles in cellular processes.
View Article and Find Full Text PDFPediatr Pulmonol
January 2025
Department of Pediatrics and Adolescent Medicine, Danish PCD Centre, Danish Pediatric Pulmonary Service, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
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