MRC National Institute for Medical Research, London
Science for Health
Sila Konur Ultanir group project:
Mechanistic understanding of CDKL5 function
Cyclin- dependent kinase like 5 (Cdkl5) also known as serine threonine kinase 9 (Stk9) is a member of cyclin-dependent kinase family of serine/threonine protein kinases. Mutations in cdkl5 gene have been associated with severe neurodevelopmental disorders such as Infantile Spasms, West Syndrome and atypical Rett syndrome. Cdkl5 gene is on the X chromosome and mutations in cdkl5 affects girls.
Although rapidly growing evidence implies cdkl5 in these developmental disorders, the current understanding of the biological function of CDKL5 is limited. CDKL5 is heavily expressed in the brain during development and in adult. In cortical neurons CDKL5 shuttles between nucleus and cytoplasm and loss of CDKL5 function causes reduced dendrite arborization. The function of cdkl5 in synaptic development and dendritic spine morphogenesis has not been investigated. More importantly the molecular mechanisms by which CDKL5 exert its functions is unknown.
A direct and unbiased screen to identify the phosphorylation targets of CDKL5 would address its molecular functions. We propose to use our kinase substrate identification method to reveal the substrates of CDKL5 and the phosphorylation sites. Our next goal is to investigate the significance of CDKL5 and its substrates in neuronal development using morphological and physiological methods in cultures and using mouse models.
Ultanir group
Recent publications
Research projects
- Functions of novel NDR1/2 substrates in neural development
- Mechanistic understanding of CDKL5 function
Ultanir biography
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