Caught Nek-ing: cilia and centrioles.

Area of Science:

• Cell Biology
• Evolutionary Biology
• Genetics

Background:

• The Nek (Never in mitosis gene A-related kinase) family of cell-cycle kinases is conserved across eukaryotes but many members remain poorly understood.
• Understanding the evolutionary history and functional conservation of Nek proteins is crucial for deciphering their roles in fundamental cellular processes.

Purpose of the Study:

• To investigate the evolutionary relationships of Nek kinases across different eukaryotic clades.
• To explore whether microbial Neks can illuminate ancestral functions retained in vertebrate Neks.
• To connect Nek protein functions with their roles in cell division and human diseases.

Main Methods:

• Comparative analysis of Nek protein sequences across eukaryotic clades.
• Phylogenetic and statistical analyses to infer coevolutionary patterns.
• Integration of functional data from microbial and vertebrate systems.

Main Results:

• Nek proteins exhibit diverse roles, with some (Nek2/NIMA relatives) involved in nuclear envelope breakdown and centromere separation, while others (Nek6, Nek7, Nek9) regulate mitosis.
• Nek1 and Nek8 are associated with polycystic kidney disease.
• Statistical analyses revealed that the Nek kinase family coevolved with centrioles, which serve as microtubule-organizing centers and basal bodies.

Conclusions:

• The evolutionary trajectory of Nek kinases, particularly their coevolution with centrioles, provides significant insights into their cellular functions.
• Studying microbial Neks offers valuable perspectives on the ancestral roles of these kinases and their implications in human diseases.