Life Sciences & Biotechnology
Title : | Elucidating the role of primary microcephaly-associated CPAP G-box domain in regulating centriole length and number |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Priyanka Singh, Indian Institute Of Technology (IIT) Jodhpur, Rajasthan |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | priyankasingh@iitj.ac.in |
Equipments : | Multimode Microplate reader |
Details
Executive Summary : | Centrioles, microtubule-based cylindrical structures, are at the core of major microtubule-organizing centers called centrosomes in proliferating cells. They transition to basal bodies in quiescent cells to generate cilia or flagella, making centriole organization crucial for cell division, signaling, and motility. Mutations in core centriole proteins that result in abnormal centrosomes or their architecture have been associated with human diseases like cancers, neurodevelopmental disorders, and ciliopathies. Centriole microtubules share the same architecture as cytoplasmic microtubules but grow slowly and progressive. The centriole protein CPAP is an important molecular linker between the centriole proteinaceous inner cartwheel-like structure and the outer centriole microtubule triplet. Overexpression of CPAP causes overly long centrioles. CPAP has three major conserved regions: PN2-3, A5N, and the G-box region. PN2-3 interacts with the tubulin β subunit, destabilizing centriole microtubules, contributing to their slow and progressive growth. The A5N domain stabilizes microtubules, while the G-box domain regulates centriole length and number. In neurodevelopmental disorders, the autosomal recessive primary microcephaly-6 (MCPH6) mutation falls in the G-box of CPAP, leading to an increase in centriole length. Recent work highlights the role of the G-box in regulating centriole length and number, with another microcephaly-associated mutation causing an increase in centriole number. These findings provide insights into pathways linking centrosome organization defects to diseases like primary microcephaly. |
Total Budget (INR): | 57,97,264 |
Organizations involved