Biochemical controls: building cilia (Introduction)

by David Turell , Friday, August 25, 2023, 20:33 (247 days ago) @ David Turell

Important in many organs:

https://phys.org/news/2023-08-secrets-cilia-nsl-complex-intraciliary.html

"Cilia are thin, eyelash-like extensions on the surface of cells. They perform a wide variety of functions, acting as mechanosensors or chemosensors, and play a crucial role in many signaling pathways.

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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.

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"The NSL complex is a potent epigenetic modifier that regulates thousands of genes in fruit flies, mice, and humans. However, most of the functions of the NSL complex remain mysterious and have only recently begun to be elucidated. "Previous research from our lab indicates that the NSL complex controls many pathways critical for organismal development and cellular homeostasis," says Akhtar, Director at the MPI of Immunobiology and Epigenetics in Freiburg.

"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.

"'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. In the study, the researchers used mouse cells to determine the functional consequences of the loss of the NSL complex in the cells.

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 Akhtar.

"Although tiny protrusions, these sensory organelles are incredibly important to cells. Ciliopathies, which affect organs as diverse as the kidney, liver, eye, ear, and central nervous system, remain challenging for biological and clinical studies. The researchers at the Max Planck Institute in Freiburg hope that their analysis of the role of the NSL complex has provided important insights into the regulation of these organelles and the genes associated with them, thus contributing to human health."

Comment: cilia are vital components of many organs. their construction process is irreducibly complex and must be designed all at once. Teh NSL complex is also irreducibly complex and must be designed all at once:

https://www.science.org/doi/10.1126/sciadv.adh5598

Not by chance.