Abstract
The coiled-coil domain containing 50 (CCDC50) protein is a phosphotyrosine-dependent signalling protein stimulated by epidermal growth factor. It is highly expressed in neuronal cells in the central nervous system; however, the roles of CCDC50 in neuronal development are largely unknown. In this study, we showed that the depletion of CCDC50-V2 impeded the neuronal development process, including arbor formation, spine density development, and axonal outgrowth, in primary neurons. Mechanistic studies revealed that CCDC50-V2 positively regulated the nerve growth factor receptor, while it downregulated the epidermal growth factor receptor pathway. Importantly, JNK/c-Jun activation was found to be induced by the CCDC50-V2 overexpression, in which the interaction between CCDC50-V2 and JNK2 was also observed. Overall, the present study demonstrates a novel mechanism of CCDC50 function in neuronal development and provides new insight into the link between CCDC50 function and the aetiology of neurological disorders.
Highlights
The coiled-coil domain-containing 50 (CCDC50) protein was identified as a phosphotyrosine-dependent signalling protein in epidermal growth factor (EGF)-stimulated human epidermoid carcinoma cells[1]
We show that coiled-coil domain containing 50 (CCDC50)-V2 is associated with the development of neuronal phenotypes
Our data revealed that CCDC50-V2 induces the activation of JNK/c-Jun and upregulation of nerve growth factor receptor (NGFR) signalling, which might be occurs through an interaction between CCDC50-V2 and JNK isoform 2 (JNK2)
Summary
The coiled-coil domain-containing 50 (CCDC50) protein ( termed Ymer) was identified as a phosphotyrosine-dependent signalling protein in epidermal growth factor (EGF)-stimulated human epidermoid carcinoma cells[1]. CCDC50 is dynamically expressed during inner ear development, in adults, it is prominently associated with cochlear hair cells, the functional impairment of which leads to alterations in intracortical network activities[3,12,13] This suggests that CCDC50 may have an imperative role in neuronal development, but direct evidence has not yet been reported. CCDC50-V2 induces the JNK/c-Jun activation and the positive regulation of NGFR expression, while it negatively regulates the EGFR pathway, thereby playing a crucial role in cell fate control during neural development. These findings support an important role for CCDC50-V2 in neuronal development through the regulation of signalling pathways associated with cell fate control and neuronal differentiation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
