Chibby promotes ciliary vesicle formation and basal body docking during airway cell differentiation
نویسندگان
چکیده
Airway multiciliated epithelial cells play crucial roles in the mucosal defense system, but their differentiation process remains poorly understood. Mice lacking the basal body component Chibby (Cby) exhibit impaired mucociliary transport caused by defective ciliogenesis, resulting in chronic airway infection. In this paper, using primary cultures of mouse tracheal epithelial cells, we show that Cby facilitates basal body docking to the apical cell membrane through proper formation of ciliary vesicles at the distal appendage during the early stages of ciliogenesis. Cby is recruited to the distal appendages of centrioles via physical interaction with the distal appendage protein CEP164. Cby then associates with the membrane trafficking machinery component Rabin8, a guanine nucleotide exchange factor for the small guanosine triphosphatase Rab8, to promote recruitment of Rab8 and efficient assembly of ciliary vesicles. Thus, our study identifies Cby as a key regulator of ciliary vesicle formation and basal body docking during the differentiation of airway ciliated cells.
منابع مشابه
Basal body docking in airway ciliated cells
Multiciliated cells (MCCs) in the respiratory epithelium play crucial roles in the innate defense system against airborne pathogens and pollutants. Each MCC possesses 200-300 cilia on their apical surface, which beat in a synchronized manner to clear mucus with foreign particles from the respiratory tract. Ciliary dysfunction leads to serious respiratory diseases including chronic infection as ...
متن کاملAltered Lung Morphogenesis, Epithelial Cell Differentiation and Mechanics in Mice Deficient in the Wnt/β-Catenin Antagonist Chibby
The canonical Wnt/β-catenin pathway plays crucial roles in various aspects of lung morphogenesis and regeneration/repair. Here, we examined the lung phenotype and function in mice lacking the Wnt/β-catenin antagonist Chibby (Cby). In support of its inhibitory role in canonical Wnt signaling, expression of β-catenin target genes is elevated in the Cby(-/-) lung. Notably, Cby protein is prominent...
متن کاملInactivation of Chibby affects function of motile airway cilia
Chibby (Cby) is a conserved component of the Wnt-beta-catenin pathway. Cby physically interacts with beta-catenin to repress its activation of transcription. To elucidate the function of Cby in vertebrates, we generated Cby(-/-) mice and found that after 2-3 d of weight loss, the majority of mice die before or around weaning. All Cby(-/-) mice develop rhinitis and sinusitis. When challenged wit...
متن کاملConditional knockout mice for the distal appendage protein CEP164 reveal its essential roles in airway multiciliated cell differentiation
Multiciliated cells of the airways, brain ventricles, and female reproductive tract provide the motive force for mucociliary clearance, cerebrospinal fluid circulation, and ovum transport. Despite their clear importance to human biology and health, the molecular mechanisms underlying multiciliated cell differentiation are poorly understood. Prior studies implicate the distal appendage/transitio...
متن کاملRhoA-mediated apical actin enrichment is required for ciliogenesis and promoted by Foxj1.
Programs that direct cellular differentiation are dependent on the strict temporal expression of regulatory factors that can be provided by Rho GTPases. Ciliogenesis is a complex sequence of events involving the generation and docking of basal bodies at the apical membrane, followed by ciliary axoneme generation. Although a cilia proteome has been assembled, programs that direct ciliated cell d...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 207 شماره
صفحات -
تاریخ انتشار 2014