The adherens junctions (AJs) and tight junctions (TJs) provide critical adhesive contacts between neighboring epithelial cells and are crucial for epithelial adhesion, integrity, and barrier functions in a wide variety of tissues and organisms. The striatin protein family, which are part of the striatin interaction phosphatases and kinases complex, are multidomain scaffolding proteins that play important biologic roles. We have previously shown that striatin colocalizes with the tumor suppressor protein adenomatous polyposis coli in the TJs of epithelial cells. Here we show that striatin affects junction integrity and cell migration, probably through a mechanism that involves the adhesion molecule E‐cadherin. Cells engaged in cell—cell adhesion expressed a high MW‐modified form of striatin that forms stable associations with detergent‐insoluble, membrane‐bound cellular fractions. In addition, striatin has recently been suggested to be a target of the poly (ADP‐ribose) polymerases Tankyrase 1, and we have found that striatin interacts with Tankyrase 1 and is subsequently poly‐ADP‐ribosylated. Taken together, our results suggest that striatin is a novel cell—cell junctional protein that functions to maintain correct cell adhesion and may have a role in establishing the relationship between AJs and TJs that is fundamental for epithelial cell—cell adhesion.—Lahav‐Ariel, L., Caspi, M., Nadar‐Ponniah, P. T., Zelikson, N., Hofmann, I., Hanson, K. K., Franke, W. W., Sklan, E. H., Avraham, K. B., Rosin‐Arbesfeld, R. Striatin is a novel modulator of cell adhesion. FASEB J. 33, 4729–4740 (2019). www.fasebj.org

Background: Meniere’s disease (MD) is a set of rare disorders that affects >4 million people worldwide. Individuals with MD suffer from episodes of vertigo associated with fluctuating sensorineural hearing loss and tinnitus. Hearing loss can involve one or both ears. Over 10% of the reported cases are observed in families, suggesting its significant genetic contribution. The condition is polygenic with >20 genes, and several patterns of inheritance have been reported, including autosomal dominant, autosomal recessive, and digenic inheritance across multiple MD families. Preclinical research using animal models has been an indispensable tool for studying the neurophysiology of the auditory and vestibular systems and to get a better understanding of the functional role of genes that are involved in the hearing and vestibular dysfunction. While mouse models are the most used preclinical model, this review analyzes alternative animal and non-animal models that can be used to study MD genes. Methods: A literature search of the 21 genes reported for familial MD and the preclinical models used to investigate their functional role was performed. Results: Comparing the homology of proteins encoded by these genes to other model organisms revealed Drosophila and zebrafish as cost-effective models to screen multiple genes and study the pathophysiology of MD. Conclusions: Murine models are preferred for a quantitative neurophysiological assessment of hearing and vestibular functions to develop drug or gene therapy.