Biochemical controls: cells form cilia (Introduction)

by David Turell , Sunday, August 27, 2023, 18:00 (244 days ago) @ David Turell

To communicate and for other functions:

https://www.sciencedaily.com/releases/2023/08/230825140357.htm

"The NSL (non-specific lethal) complex regulates thousands of genes in fruit flies and mammals. Silencing the NSL genes leads to the death of the organism, which gave the complex its curious name. Researchers have now discovered that the genes regulated by the NSL complex also include genes of the intraciliary transport system. This enables different cell types to form cilia on their surface, which are important for cell communication. The study shows that these genes are 'switched on' by the NSL complex, regardless of whether a particular cell has cilia or not. The researchers found that this class of cilia-associated genes is crucial for the function of podocytes. This is a highly specialized cell type of the kidney that, paradoxically, does not have cilia. These findings have important implications for ciliopathies and kidney disease.

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"The proper assembly, maintenance, and function of cilia rely on a process called "intraciliary transport." Components of the intraciliary transport system "walk" on the microtubule to deliver cargo between the cell body and the ciliary tip to ensure a constant supply of materials...In their recent study in the journal Science Advances, the lab of Asifa Akhtar identified the NSL complex as a transcriptional regulator of genes known for their roles in the intraciliary transport system of cilia across multiple cell types.

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"The complex comprises several proteins and is a histone acetyltransferase (HAT) complex that prepares the genes for activation. "Think of gene regulation as a team effort with different players. One important player is the NSL complex. It puts special marks on the histone proteins on which the DNA is wrapped around in the nucleus, like putting up green flags. These flags tell other regulators to switch on specific genes. We now found that the NSL complex does exactly this for a group of genes linked to moving materials within cilia," says Tsz Hong Tsang, the first author of the study.

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"The intraciliary transport system is essential because it is needed to build a functional cilium. The cell uses the intraciliary transport system to move material from the cilium base to the growing tip -- similar to building a tower.

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"They found that fibroblast cells lacking the NSL complex protein KANSL2 could not activate the transport genes nor assemble cilia. "As cilia are the sensory and signaling hubs for cells, loss of KANSL2 leads to the inability of cells to activate the sonic hedgehog signaling pathway, which plays important roles in the regulation of embryonic development, cell differentiation, and maintenance of adult tissues as well as cancer," says Asifa Akhtar."

Comment: my usual view is that this degree of complexity requires a designing mind.