STARD9/Kif16a is a novel mitotic kinesin and antimitotic target

Abstract

Proper cell division requires the formation of the microtubule-based mitotic spindle, which mediates the dynamic movement and alignment of chromosomes to the metaphase plate and their equal transmission to daughter cells. Kinesins are molecular motors that utilize ATP hydrolysis to perform their functions and are instrumental in spindle assembly and function. Of the over 45 kinesins encoded in the human genome, only two are specifically enriched at the centrioles, Kif24 at the mother centriole and STARD9/Kif16a at the daughter centriole. While Kif24 possesses centriolar microtubule-depolymerizing activity and has been implicated in regulating cilia formation, our recent study implicates STARD9 in maintaining pericentriolar material (PCM) cohesion during early mitosis. However, very little is known about how STARD9 performs its function, including the mechanisms that recruit or retain STARD9 at the centrioles and how it cooperates with centrosome components to regulate PCM stability. Additionally, the signals leading to apoptosis in the absence of STARD9 remain to be explored.

Figure 1. The role of STARD9/Kif16a during cell division. (A) STARD9 is a large ~517 kDa modular protein with an N-terminal kinesin motor domain, an FHA phosphoprotein binding domain, and a C-terminal START lipid/sterol binding domain. (B) Localization of STARD9 to the centrosome. Note that STARD9 is enriched at the daughter centriole. (C) The localization of STARD9 to the daughter centriole occurs during centrosome maturation (after centrosome duplication but before centrosome separation) and is required for PCM cohesion and bipolar spindle assembly.