ALMS1 Regulates TGF-β Signaling and Morphology of Primary Cilia

María Álvarez-Satta; Mauro Lago-Docampo; Brais Bea-Mascato; Carlos Solarat; Sheila Castro-Sánchez; Søren T Christensen; Diana Valverde

doi:10.3389/fcell.2021.623829

ALMS1 Regulates TGF-β Signaling and Morphology of Primary Cilia

Front Cell Dev Biol. 2021 Feb 1:9:623829. doi: 10.3389/fcell.2021.623829. eCollection 2021.

Authors

María Álvarez-Satta^{1

2}, Mauro Lago-Docampo^{1

2}, Brais Bea-Mascato^{1

2}, Carlos Solarat^{1

2}, Sheila Castro-Sánchez^{1

2}, Søren T Christensen³, Diana Valverde^{1

2}

Affiliations

¹ CINBIO, Universidade de Vigo, Vigo, Spain.
² Instituto de Investigación Sanitaria Galicia Sur (IIS Galicia Sur), Hospital Álvaro Cunqueiro, Vigo, Spain.
³ Department of Biology, Section of Cell Biology and Physiology, The August Krogh Building, University of Copenhagen, Copenhagen, Denmark.

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.

Keywords: ALMS1; Alström syndrome (AS); TGF-β/BMP signaling; ciliary length; ciliary morphology; ciliopathies; hTERT RPE-1 cells; primary cilium.