LUZP1, a novel regulator of primary cilia and the actin cytoskeleton, is a contributing factor in Townes-Brocks Syndrome.

Primary cilia are sensory organelles crucial for cell signaling during development and organ homeostasis. Cilia arise from centrosomes and their formation and function is governed by numerous factors. Through our studies on Townes-Brocks Syndrome (TBS), a rare disease linked to abnormal cilia formation in human fibroblasts, we uncovered the leucine-zipper protein LUZP1 as an interactor of truncated SALL1, a dominantly-acting protein causing the disease. Using TurboID proximity labeling and pulldowns, we show that LUZP1 associates with factors linked to centrosome and actin filaments. Here, we show that LUZP1 is a cilia regulator. It localizes around the centrioles and to actin cytoskeleton. Loss of LUZP1 reduces F-actin levels, facilitates ciliogenesis and alters Sonic Hedgehog signaling, pointing to a key role in cytoskeleton-cilia interdependency. Truncated SALL1 increases the ubiquitin proteasome-mediated degradation of LUZP1. Together with other factors, alterations in LUZP1 may be contributing to TBS etiology.

Primary cilia are the 'antennae' of animal cells: these small, flexible protrusions emerge from the surface of cells, where they help to sense and relay external signals. Cilia are assembled with the help of the cytoskeleton, a dynamic network of mesh-like filaments that spans the interior of the cell and controls many different biological processes. If cilia do not work properly, human diseases called ciliopathies can emerge. Townes-Brocks Syndrome (TBS) is an incurable disease that presents a range of symptoms such as malformations of the toes or fingers, hearing impairment, and kidney or heart problems. It is caused by a change in the gene that codes for a protein called SALL1, and recent work has also showed that the cells of TBS patients have defective cilia. In addition, this prior research identified a second protein that interacted with the mutant version of SALL1; called LUZP1, this protein is already known to help maintain the cytoskeleton. In this study, Bozal-Basterra et al. wanted to find out if LUZP1 caused the cilia defects in TBS. First, the protein was removed from mouse cells grown in the laboratory, which dramatically weakened the cytoskeleton. In keeping with this observation, both the number of cilia per cell and the length of the cilia were abnormal. Cells lacking LUZP1 also had defects in a signalling process that transmits signals received by cilia to different parts of the cell. All these defects were previously observed in cells isolated from TBS patients. In addition, LUZP1-deficient mouse cells showed the same problems with their cilia and cytoskeleton as the cells from individuals with TBS. Crucially, the cells from human TBS patients also had much lower levels of LUZP1 than normal, suggesting that the protein may contribute to the cilia defects present in this disease. The work by Bozal-Basterra et al. sheds light on how primary cilia depend on the cytoskeleton, while also providing new insight into TBS. In the future, this knowledge could help researchers to develop therapies for this rare and currently untreatable disease.

Efficiency of a cleaning protocol for the removal of enterotoxigenic Staphylococcus aureus strains in dairy plants.

Staphylococci are considered a major concern in dairy plants mainly due to the intensive production flow, automation of processing plants and increased demand in the microbiological quality of dairy products. This study aimed to identify S. aureus strains isolated from three Brazilian dairy plants, evaluate the influence of time, temperature and contact surface on the bacterial adhesion process, as well as the efficiency of simulated hygiene and sanitation protocol in removing adhered cells. For genotypic analyses, the presence of icaA and icaD in strains was evaluated. Adherence assays were performed in biofilm reactor, comparing the influence of 2 temperatures (5°C and 35°C), 2 surfaces (stainless steel and polypropylene) and 4 contact times (3, 6, 12h and post-sanitization). To evaluate the process effectiveness in removing adhered cells, neutral detergent and sanitizing agent based on sodium hypochlorite were used in order to simulate the situation observed in one of the dairy plants analyzed. The presence of icaA and icaD genes was determined in 75.3% and 77.6% of strains, respectively; 70.6% of isolates showed both genes, whereas 17.6% showed no genes. Genes for enterotoxin production were found in all samples, relating to SEG and SEH toxins. The number of cells adhered on both surfaces was about 3 and 6 log10 CFU/cm2 at temperatures of 5°C and 35°C, respectively, for most situations evaluated, with significant increase over the evaluation period. In general, the temperature of 35°C favored greater adherence of S. aureus. At 5°C, there was a considerable number of adhered cells, but in populations significantly lower than those observed at 35°C. The cleaning and sanitizing protocol was ineffective in removing adhered cells; better performance of sodium hypochlorite was observed at 5°C, which should be related to lower adherence observed at this temperature. Thus, the process was not able to reduce the number of S. aureus bacteria adhered on both surfaces to safe levels under the conditions evaluated.