AUTHOR=Álvarez-Satta María , Lago-Docampo Mauro , Bea-Mascato Brais , Solarat Carlos , Castro-Sánchez Sheila , Christensen Søren T. , Valverde Diana TITLE=ALMS1 Regulates TGF-β Signaling and Morphology of Primary Cilia JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=9 YEAR=2021 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.623829 DOI=10.3389/fcell.2021.623829 ISSN=2296-634X ABSTRACT=

In this study, we aimed to evaluate the role of ALMS1 in the morphology of primary cilia and regulation of cellular signaling using a knockdown model of the hTERT-RPE1 cell line. ALMS1 depletion resulted in the formation of longer cilia, which often displayed altered morphology as evidenced by extensive twisting and bending of the axoneme. Transforming growth factor beta/bone morphogenetic protein (TGF-β/BMP) signaling, which is regulated by primary cilia, was similarly affected by ALMS1 depletion as judged by reduced levels of TGFβ-1-mediated activation of SMAD2/3. These results provide novel information on the role of ALMS1 in the function of primary cilia and processing of cellular signaling, which when aberrantly regulated may underlie Alström syndrome.