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Ciliated bronchial epithelium 1 (CBE1) is a microtubule-associated protein localized to the manchette and developing flagellum during spermiogenesis, and associated with sperm maturation arrest in humans. It was hypothesized that CBE1 functions in microtubule-mediated transport mechanisms and sperm tail formation. To test this hypothesis, we analysed Cbe1 expression and localization during spermiogenesis, and in mouse IMCD3 cells as a model of ciliogenesis. Further, we generated and analysed the fertility of a Cbe1 mutant mouse line. Mice containing a homozygous deletion in the long forms of Cbe1 were born at a lower frequency than predicted by Mendelian inheritance, however, adult male mice were fertile. An in-depth analysis of the Cbe1 gene revealed alternative transcript variants, which were not affected by the exon 2 mutation. To assess whether short variants compensate for the loss of long variants, exons 2 and 4 (which affect all variants) were individually mutated in IMCD3 cells and the effect on cell proliferation and ciliogenesis analysed. In wild type IMCD3 cells, both variants were upregulated during cilia assembly. CBE1 protein was not a structural component of cilia, rather, CBE1 localised to the mitochondria and the contractile ring of dividing IMCD3 cells. While IMCD3 cells carrying the mutation in long variants showed no phenotypic alterations, the mutation in exon 4 resulted in a significantly decreased proliferation rate. This study reveals that long isoforms of CBE1 are not essential for male fertility. Data, however, suggests that CBE1 is associated to intra-manchette transport and mid-piece formation of the sperm tail.

CBE1 is a manchette and mitochondria associated protein with a potential role in somatic cell proliferation