EML4 and NUDC in mitotic spindle formation

EML4 and NUDC in mitotic spindle formation EML4 and NUDC proteins are required for mitotic spindle formation, attachment of spindle microtubule ends to kinetochores, and alignment of mitotic chromosome at the metaphase plate. EML4 is a WD40 family protein that binds to interphase microtubules and stabilizes them (Houtman et al. 2007, Adib et al. 2019). At mitotic entry, EML4 undergoes phosphorylation (Pollmann et al. 2006, Adib et al. 2019) by serine/threonine kinases NEK6 and NEK7, leading to its dissociation from microtubules, which is necessary for the assembly of a dynamic mitotic spindle (Adib et al. 2019). EML4, through its WD40 repeats, interacts with NUDC and recruits it to the kinetochores of the mitotic spindle (Chen et al. 2015). It is possible that other mitotic kinases, besides NEK6 and NEK7, also phosphorylate EML4. Phosphorylation of different residues of EML4 could reduce or increase affinity of EML4 for specific subpopulations of microtubules in mitosis.
A recurrent genomic rearrangement, reported in about 5% cases of non-small cell lung cancer (NSCLC) fuses the N-terminal portion of EML4 with the C-terminal portion of ALK (anaplastic lymphoma kinase), resulting in a constitutively active ALK (Soda et al. 2007, Richards et al. 2015).